Alcohol-dependent patients receiving specialised outpatient care: an overview of gender issues

OBJECTIVE: The objective of the present study, with focus on gender, was aimed at evaluating alcohol-dependent individual in terms of socio-demographic variables related to alcohol consumption and therapeutic interventions. METHODS: This is a retrospective cross-sectional study of 1,051 patients (833 men and 218 women), with diagnosis of alcohol dependence syndrome, according to ICD-10 criteria, who had sought treatment for the first time at a specialised health centre between 2000 and 2006. RESULTS: The results showed that women, compared to men, are more likely to be unemployed and without partner, in addition to having higher educational level, latter age of alcohol initiation, needing less outpatient alcohol detoxification program, consuming more fermented beverage, presenting less psychiatric comorbidities, and using less coadjutant medications during treatment. CONCLUSION: We can state that some peculiarities exist permeating both gender and alcohol consumption. A further focus on the characteristics of each population is needed to facilitate the adequate use of therapeutic interventions according to gender specificities.

Factors affecting phosphate fixation in soils of the state of São Paulo

A laboratory experiment was carried out to study the effects of chemical and physical characteristics of the soil on the phosphate fixing capacity. One hundred samples collected from various localities were at first characterized chemically and their particlesize distribution determined. They were then tested as to their phosphate fixing capacities. The results obtained were statistically analysed by means of both simple linear and multiple correlation. The following conclusions could be drawn: 1. simple linear regression analysis indicated that % C, exchangeable Al+3, CEC, % clay, pH and % sand were the soil characteristics which significantly affected phosphate fixing capacity of São Paulo State soils; 2. multiple linear regression analysis indicated that % C, exchangeable Mg(+2)9 exchangeable- Al+3 and % clay were the soil characteristics which significantly affected the phosphate fixing capacity of São Paulo State soils; 3. the phosphate phonomena fixing as they occur in the soils of the São Paulo State can be best described by the following equation: Y = -2,266 - 3,484 + 3,514 + 5,559 + 1,005 %C Mg+2 Al+3 % clay exchangeable exchangeable 4. phosphate fixation in the soil is affected by the combined effects of both soil chemical and physical characteristics.

The relative growth and sexual maturity of the freshwater crab Dilocarcinus pagei (Brachyura, Trichodactylidae) in the northwestern region of the state of São Paulo

The aim of the present study was to determine the size at sexual maturity in the freshwater crab Dilocarcinus pagei Stimpson, 1861, from a population located in Mendonça, state of São Paulo, Brazil. The crabs were sampled monthly (July 2005 to June 2007), at Barra Mansa reservoir. The specimens were captured manually or in sieves passed through the aquatic vegetation. The crabs were captured and separated by sex based on morphology of the pleon and on the number of pleopods. The following dimensions were measured: carapace width (CW); carapace length (CL); propodus length (PL); and abdomen width (AW). The morphological analysis of the gonads was used to identify and categorize individuals according to their stage of development. The morphological maturity was estimated based on the analysis of relative growth based on the allometric equation y = ax b. The gonadal maturity was based on the morphology of the gonads by the method CW50 which indicates the size at which 50% of the individuals in the population showed gonads morphologically mature to reproduction. The biometric relationships that best demonstrated the different patterns of growth for the juvenile and adult stages were CW vs. PL for males and CW vs. AW for females (p<0.001). Based on these relationships, the estimated value to morphological sexual maturity was 21.5 mm (CW) in males and 19.7 mm (CW) in females. The determination of the size at sexual maturity and the adjustment of the data based on the logistic curve (CW50) resulted in a size of 38.2 mm for males and 39.4 mm for females (CW). Based on the data obtained for sexual maturity for D. pagei, we can estimate a minimum size for capture of 40 mm (CW). This minimum size allows at least half of the population to reproduce and retains the juveniles and a portion of the adults in the population.

Contractive metrics for a Boltzmann equation for granular gases: diffusive equilibriaThe Patterson-Sullivan embedding and minimal volume entropy for outer space

We quantify the long-time behavior of a system of (partially) inelastic particles in a stochastic thermostat by means of the contractivity of a suitable metric in the set of probability measures. Existence, uniqueness, boundedness of moments and regularity of a steady state are derived from this basic property. The solutions of the kinetic model are proved to converge exponentially as t→ ∞ to this diffusive equilibrium in this distance metrizing the weak convergence of measures. Then, we prove a uniform bound in time on Sobolev norms of the solution, provided the initial data has a finite norm in the corresponding Sobolev space. These results are then combined, using interpolation inequalities, to obtain exponential convergence to the diffusive equilibrium in the strong L¹-norm, as well as various Sobolev norms.

Rigorous derivation of a nonlinear diffusion equation as fast-reaction limit of a continuous coagulation-fragmentation model with diffusion

Weak solutions of the spatially inhomogeneous (diffusive) Aizenmann-Bak model of coagulation-breakup within a bounded domain with homogeneous Neumann boundary conditions are shown to converge, in the fast reaction limit, towards local equilibria determined by their mass. Moreover, this mass is the solution of a nonlinear diffusion equation whose nonlinearity depends on the (size-dependent) diffusion coefficient. Initial data are assumed to have integrable zero order moment and square integrable first order moment in size, and finite entropy. In contrast to our previous result [CDF2], we are able to show the convergence without assuming uniform bounds from above and below on the number density of clusters.

Synaptobrevin N-terminally bound to syntaxin-SNAP-25 defines the primed vesicle state in regulated exocytosis.

Rapid neurotransmitter release depends on the ability to arrest the SNAP receptor (SNARE)-dependent exocytosis pathway at an intermediate "cocked" state, from which fusion can be triggered by Ca(2+). It is not clear whether this state includes assembly of synaptobrevin (the vesicle membrane SNARE) to the syntaxin-SNAP-25 (target membrane SNAREs) acceptor complex or whether the reaction is arrested upstream of that step. In this study, by a combination of in vitro biophysical measurements and time-resolved exocytosis measurements in adrenal chromaffin cells, we find that mutations of the N-terminal interaction layers of the SNARE bundle inhibit assembly in vitro and vesicle priming in vivo without detectable changes in triggering speed or fusion pore properties. In contrast, mutations in the last C-terminal layer decrease triggering speed and fusion pore duration. Between the two domains, we identify a region exquisitely sensitive to mutation, possibly constituting a switch. Our data are consistent with a model in which the N terminus of the SNARE complex assembles during vesicle priming, followed by Ca(2+)-triggered C-terminal assembly and membrane fusion.

Isolation of fungi from nature in the region of Botucatu, state of São Paulo, Brazil, an endemic area of paracoccidioidomycosis

In an attempt to isolate Paracoccidioides brasiliensis from nature 887 samples of soil from Botucatu, SP, Brazil, were collected cultured in brain heart infusion agar supplemented with dextrose, in potato dextrose agar and in yeast extract starch dextrose agar, all with antibiotics, at 25º and 37ºC. Five thermo-dependent dimorphic fungi morphologically resembling P. brasiliensis were isolated; two from armadillo holes; further studies of the biology, antigenicity and genetic features of the five dimorphic fungi are necessary to clarify their taxonomy and their possible relation to P. brasiliensis. In addition, 98 dematiaceous fungi and 581 different species of Aspergillus spp. were also isolated. Our findings emphasize that armadillos and their environment are associated with thermo-dimorphic fungi and confirm the ubiquity of pathogenic dematiaceous fungi and Aspergillus spp.

Frequency-dependent sexual selection with respect to offspring fitness returns is consistent with predictions from rock-paper-scissors dynamics in the European common lizard

Genetic polymorphism can be maintained over time by negative frequency-dependent (FD) selection induced by Rock-paper-scissors (RPS) social systems. RPS games produce cyclic dynamics, and have been suggested to exist in lizards, insects, isopods, plants, and bacteria. Sexual selection is predicted to accentuate the survival of the future progeny during negative FD survival selection. More specifically, females are predicted to select mates that produce progeny genotypes that exhibit highest survival during survival selection imposed by adult males. However, no empirical evidence demonstrates the existence of FD sexual selection with respect to fitness payoffs of genetic polymorphisms. Here we tested this prediction using the common lizard Zootoca vivipara, a species with three male color morphs (orange, white, yellow) that exhibit morph frequency cycles. In a first step we tested the congruence of the morph frequency change with the predicted change in three independent populations, differing in male color morph frequency and state of the FD morph cycle. Thereafter we ran standardized sexual selection assays in which we excluded alternative mechanisms that potentially induce negative FD selection, and we quantified inter-sexual behavior. The patterns of sexual selection and the observed behavior were in line with context-dependent female mate choice and male behavior played a minor role. Moreover, the strength of the sexual selection was within the magnitude of selection required to produce the observed 3-4-year and 6-8 year morph frequency cycles at low and high altitudes, respectively. In summary, the study provides the first experimental evidence that underpins the crucial assumption of the RPS games suggested to exist in lizards, insects, isopods, and plants; namely, that sexual selection produces negative-FD selection. This indicates that sexual selection, in our study exert by females, might be a crucial driver of the maintenance of genetic polymorphisms.

Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells.

The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are insulinotropic factors released from the small intestine to the blood stream in response to oral glucose ingestion. The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking. We defined the exon-intron boundaries of the human GIP receptor, made a mutational analysis of the gene and identified two amino acid substitutions, A207 V and E354Q. In an association study of 227 Caucasian Type II diabetic patients and 224 matched glucose tolerant control subjects, the allelic frequency of the A207 V polymorphism was 1.1% in Type II diabetic patients and 0.7% in control subjects (p = 0.48), whereas the allelic frequency of the codon 354 polymorphism was 24.9% in Type II diabetic patients versus 23.2% in control subjects. Interestingly, the glucose tolerant subjects (6% of the population) who were homozygous for the codon 354 variant had on average a 14% decrease in fasting serum C-peptide concentration (p = 0.01) and an 11% decrease in the same variable 30 min after an oral glucose load (p = 0.03) compared with subjects with the wild-type receptor. Investigation of the function of the two GIP receptor variants in Chinese hamster fibroblasts showed, however, that the GIP-induced cAMP formation and the binding of GIP to cells expressing the variant receptors were not different from the findings in cells expressing the wildtype GIP receptor. In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts. The finding of an association between homozygosity for the codon 354 variant and reduced fasting and post oral glucose tolerance test (OGTT) serum C-peptide concentrations, however, calls for further investigations and could suggest that GIP even in the fasting state regulates the beta-cell secretory response.

Use-dependent block of the voltage-gated Na+ channel by tetrodotoxin and saxitoxin: Effect of pore mutations that change ionic selectivity.

Voltage-gated Na(+) channels (NaV channels) are specifically blocked by guanidinium toxins such as tetrodotoxin (TTX) and saxitoxin (STX) with nanomolar to micromolar affinity depending on key amino acid substitutions in the outer vestibule of the channel that vary with NaV gene isoforms. All NaV channels that have been studied exhibit a use-dependent enhancement of TTX/STX affinity when the channel is stimulated with brief repetitive voltage depolarizations from a hyperpolarized starting voltage. Two models have been proposed to explain the mechanism of TTX/STX use dependence: a conformational mechanism and a trapped ion mechanism. In this study, we used selectivity filter mutations (K1237R, K1237A, and K1237H) of the rat muscle NaV1.4 channel that are known to alter ionic selectivity and Ca(2+) permeability to test the trapped ion mechanism, which attributes use-dependent enhancement of toxin affinity to electrostatic repulsion between the bound toxin and Ca(2+) or Na(+) ions trapped inside the channel vestibule in the closed state. Our results indicate that TTX/STX use dependence is not relieved by mutations that enhance Ca(2+) permeability, suggesting that ion-toxin repulsion is not the primary factor that determines use dependence. Evidence now favors the idea that TTX/STX use dependence arises from conformational coupling of the voltage sensor domain or domains with residues in the toxin-binding site that are also involved in slow inactivation.

INK4a/Arf is required for suppression of EGFR/DeltaEGFR(2-7)-dependent ERK activation in mouse astrocytes and glioma.

Amplification of the epidermal growth factor receptor (EGFR) or expression of its constitutively activated mutant, DeltaEGFR(2-7), in association with the inactivation of the INK4a/Arf gene locus is a frequent alteration in human glioblastoma. The notion of a cooperative effect between these two alterations has been demonstrated in respective mouse brain tumor models including our own. Here, we investigated underlying molecular mechanisms in early passage cortical astrocytes deficient for p16(INK4a)/p19(Arf) or p53, respectively, with or without ectopic expression of DeltaEGFR(2-7). Targeting these cells with the specific EGFR inhibitor tyrphostin AG1478 revealed that phosphorylation of ERK was only abrogated in the presence of an intact INK4a/Arf gene locus. The sensitivity to inhibit ERK phosphorylation was independent of ectopic expression of DeltaEGFR(2-7) and independent of the TP53 status. This resistance to downregulate the MAPK pathway in the absence of INK4a/Arf was confirmed in cell lines derived from our mouse glioma models with the respective initial genetic alterations. Thus, deletion of INK4a/Arf appears to keep ERK in its active, phosphorylated state insensitive to an upstream inhibitor specifically targeting EGFR/DeltaEGFR(2-7). This resistance may contribute to the cooperative tumorigenic effect selected for in human glioblastoma that may be of crucial clinical relevance for treatments specifically targeting EGFR/DeltaEGFR(2-7) in glioblastoma patients.

A Ca2+/H+ antiport system driven by the tonoplast pyrophosphate-dependent proton pump from maize roots.

Calcium uptake by tonoplast enriched membrane vesicles from maize (Zea mays L. cv. LG 11) primary roots was studied. A pH gradient, measured by the fluorescence quenching of quinacrine, was generated across sealed vesicles driven by the pyrophosphate-dependent proton pump. The fluorescence quenching was strongly inhibited by Ca2+; moreover, when increasing Ca2+ concentrations were added to vesicles at steady-state, a concomitant decrease in the proton gradient was observed. Ca2+ uptake using Ca-45(2+) was linear from 10 min when oxalate (10 mM) was present, while Ca2+ uptake was completely inhibited with proton ionophores (FCCP and monensin), indicating a Ca2+/H+ antiport. Membranes were further fractionated using a linear sucrose density gradient (10-45%) and were identified with marker enzymes. Ca2+ uptake co-migrated with the tonoplast pyrophosphate-dependent proton pumping, pyrophosphatase and ATPase activities: the Ca2+/H+ antiport is consequently located at the tonoplast.

A multilevel approach to understanding circadian rhythmicity : social and sleep-dependent effects in ants and mice

Résumé françaisLa majorité des organismes vivants sont soumis à l'alternance du jour et de la nuit, conséquence de la rotation de la terre autour de son axe. Ils ont développé un système interne de mesure du temps, appelé horloge circadienne, leur permettant de s'adapter et de synchroniser leur comportement et leur physiologie aux cycles de lumière. Cette dernière est considérée comme étant le signal majeur entraînant l'horloge interne et. par conséquent, les rythmes journaliers d'éveil et de sommeil. Outre sa régulation circadienne, le sommeil est contrôlé par un processus homéostatique qui détermine son besoin. La contribution de ces deux processus dans le fonctionnement cellulaire du cerveau n'a pas encore été investiguée. La mesure de l'amplitude ainsi que de la prévalence des ondes delta de l'EEG (activité delta) constitue un index très fiable du besoin de sommeil. Il a été démontré que cette activité est génétiquement déterminée et associée à un locus de trait quantitatif situé sur le chromosome 13 de la souris.Grâce à des expériences de privation de sommeil et d'analyses de transcriptome du cerveau dans trois souches de souris présentant diverses réponses à la privation de sommeil, nous avons trouvé que Homerla, localisé dans la région d'intérêt du chromosome 13, est le meilleur marqueur du besoin de sommeil. Homerla est impliqué dans la récupération de l'hyperactivité neuronale induite par le glutamate, grâce à son effet tampon sur le calcium intracellulaire. Une fonction fondamentale du sommeil pourrait donc être de protéger le cerveau et de lui permettre de récupérer après une hyperactivité neuronale imposée par une veille prolongée.De plus, nous avons montré que 2032 transcrits sont exprimés rythmiqueraent dans le cerveau de la souris, parmi lesquels seulement 391 le restent après que les animaux aient été privés de sommeil à différents moments au cours des 24 heures. Cette observation montre clairement que la plupart des changements rythmiques au niveau du transcriptome dépendent du sommeil et non de l'horloge circadienne et souligne ainsi l'importance du sommeil dans la physiologie des mammifères.La plupart des expériences concernant les rythmes circadiens ont été réalisées sur des individus isolés en négligeant l'effet du contexte social sur les comportements circadiens. Les espèces sociales, telles que les fourmis, se caractérisent par une division du travail où une répartition des tâches s'effectue entre ses membres. De plus, certaines d'entre elles doivent être pratiquées en continu comme les soins au couvain tandis que d'autres requièrent une activité rythmique comme le fourragement. Ainsi la fourmi est un excellent modèle pour l'étude de 1 influence du contexte social sur les rythmes circadiens.A ces fins, nous avons décidé d'étudier les rythmes circadiens chez une espèce de fourmi Camponotus fellah et de caractériser au niveau moléculaire son horloge circadienne. Nous avons ainsi développé un système vidéo permettant de suivre l'activité locomotrice de tous les individus d'une colonie. Nos résultats montrent que, bien que la plupart des fourmis soient arythmiques à l'intérieur de la colonie, elles développent d'amples rythmes d'activité en isolation. De plus, ces rythmes disparaissent presque aussitôt que la fourmi est réintroduite dans la colonie. Cette rythmicité observée en isolation semble être générée par l'horloge circadienne car elle persiste en condition constante (obscurité totale). Nous avons ensuite regardé si cette apparente arythmie observée dans la colonie résultait d'un effet masquant des interactions sociales sur les rythmes circadiens d'activité. Nos résultats suggèrent que l'horloge interne est fonctionnelle dans la colonie mais que l'expression de ses rythmes au niveau comportemental est inhibée par les interactions sociales. Les analyses moléculaires du statut de l'horloge dans différents contextes sociaux sont actuellement en cours. Le contexte social semble donc un déterminant majeur du comportement circadien chez la fourmi.AbstractAlmost all living organisms on earth are subjected to the alternance of day and night re-sulting from the rotation of the earth around its axis. They have evolved with an internal timing system, termed the circadian clock, enabling them to adapt and synchronize their behavior and physiology to the daily changes in light and related environmental parame¬ters. Light is thought to be the major cue entraining the circadian clock and consequently the rhythms of rest/activity. In addition to its circadian dependent timing, sleep is reg¬ulated by a homeostatic process that determines its need. The contribution of these two processes in the cellular functioning of the brain has not yet been considered. A highly reliable index of the homeostatic process of sleep is the measure of the amplitude and prevalence of the EEG delta waves (delta activity). It has been shown that sleep need, measured by delta activity, is genetically determined and associated with a Quantitative Trait Locus (QTL) located on the mouse chromosome 13. By using sleep deprivation and brain transcriptome profiling in three inbred mouse strains showing different responses to sleep loss, we found that Homerla, localized within this QTL region is the best transcrip¬tional marker of sleep need. Interestingly Homerla is primarily involved in the recovery from glutamate-induced neuronal hyperactivity by its buffering effect on intracellular cal¬cium. A fundamental function of sleep may therefore reside in the protection and recovery of the brain from a neuronal hyperactivity imposed by prolonged wakefulness.Moreover, time course gene expression experiments showed that 2032 brain tran¬scripts present a rhythmic variation, but only 391 of those remain rhythmic when mice are sleep deprived at four time points around the clock. This finding clearly suggests that most changes in gene transcription over the day are sleep-wake dependent rather than clock dependent and underlines the importance of sleep in mammalian physiology.In the second part of this PhD, I was interested in the social influence on circadian behavior. Most experiments done in the circadian field have been performed on isolated individuals and have therefore ignored the effect of the social context on circadian behav-ior. Eusocial insect species such as ants are characterized by a division of labor: colony tasks are distributed among individuals, some of them requiring continuous activity such as nursing or rhythmic ones such as foraging. Thus ants represent a suitable model to study the influence of the social context on the circadian clock and its output rhythms.The aim of this part was to address the effect of social context on circadian rhythms in the ant species Camponotus fellah and to characterize its circadian clock at the molecu¬lar level. We therefore developed a video tracking system to follow the locomotor activity of all individuals in a colony. Our results show that most ants are arrhythmic within the colony, but develop, when subjected to social isolation, strong rhythms of activity that intriguingly disappear when individuals are reintroduced into the colony. The rhythmicity observed in isolated ants seems to be driven by the circadian clock as it persists under constant conditions (complete darkness). We then tested whether the apparent arrhyth- micity in the colony stemmed from a masking effect of social interactions on circadian rhythms. Indeed, we found that circadian clocks of ants in the colony are functional but their expression at the behavioral level is inhibited by social interactions. The molecular assessment of the circadian clock functional state in the different social context is still under investigation. Our results suggest that social context is a major determinant of circadian behavior in ants.

Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model.

Glucose supply from blood to brain occurs through facilitative transporter proteins. A near linear relation between brain and plasma glucose has been experimentally determined and described by a reversible model of enzyme kinetics. A conformational four-state exchange model accounting for trans-acceleration and asymmetry of the carrier was included in a recently developed multi-compartmental model of glucose transport. Based on this model, we demonstrate that brain glucose (G(brain)) as function of plasma glucose (G(plasma)) can be described by a single analytical equation namely comprising three kinetic compartments: blood, endothelial cells and brain. Transport was described by four parameters: apparent half saturation constant K(t), apparent maximum rate constant T(max), glucose consumption rate CMR(glc), and the iso-inhibition constant K(ii) that suggests G(brain) as inhibitor of the isomerisation of the unloaded carrier. Previous published data, where G(brain) was quantified as a function of plasma glucose by either biochemical methods or NMR spectroscopy, were used to determine the aforementioned kinetic parameters. Glucose transport was characterized by K(t) ranging from 1.5 to 3.5 mM, T(max)/CMR(glc) from 4.6 to 5.6, and K(ii) from 51 to 149 mM. It was noteworthy that K(t) was on the order of a few mM, as previously determined from the reversible model. The conformational four-state exchange model of glucose transport into the brain includes both efflux and transport inhibition by G(brain), predicting that G(brain) eventually approaches a maximum concentration. However, since K(ii) largely exceeds G(plasma), iso-inhibition is unlikely to be of substantial importance for plasma glucose below 25 mM. As a consequence, the reversible model can account for most experimental observations under euglycaemia and moderate cases of hypo- and hyperglycaemia.

A constitutively active mutant of the alpha 1B-adrenergic receptor can cause greater agonist-dependent down-regulation of the G-proteins G9 alpha and G11 alpha than the wild-type receptor.

Rat 1 fibroblasts transfected to express either the wild-type hamster alpha 1B-adrenergic receptor or a constitutively active mutant (CAM) form of this receptor resulting from the alteration of amino acid residues 288-294 to encode the equivalent region of the human beta 2-adrenergic receptor were examined. The basal level of inositol phosphate generation in cells expressing the CAM alpha 1B-adrenergic receptor was greater than for the wild-type receptor, The addition of maximally effective concentrations of phenylephrine or noradrenaline resulted in substantially greater levels of inositol phosphate generation by the CAM alpha 1B-adrenergic receptor, although this receptor was expressed at lower steady-state levels than the wild-type receptor. The potency of both phenylephrine and noradrenaline to stimulate inositol phosphate production was approx. 200-fold greater at the CAM alpha 1B-adrenergic receptor than at the wild-type receptor. In contrast, endothelin 1, acting at the endogenously expressed endothelin ETA, receptor, displayed similar potency and maximal effects in the two cell lines. The sustained presence of phenylephrine resulted in down-regulation of the alpha subunits of the phosphoinositidase C-linked, pertussis toxin-insensitive, G-proteins G9 and G11 in cells expressing either the wild-type or the CAM alpha 1B-adrenergic receptor. The degree of down-regulation achieved was substantially greater in cells expressing the CAM alpha 1B-adrenergic receptor at all concentrations of the agonist. However, in this assay phenylephrine displayed only a slightly greater potency at the CAM alpha 1B-adrenergic receptor than at the wild-type receptor. There were no detectable differences in the basal rate of G9 alpha/G11 alpha degradation between cells expressing the wild-type or the CAMalpha 1B-adrenergic receptor. In both cell lines the addition of phenylephrine substantially increased the rate of degradation of these G-proteins, with a greater effect at the CAM alpha 1B-adrenergic receptor. The enhanced capacity of agonist both to stimulate second-messenger production at the CAM alpha 1B-adrenergic receptor and to regulate cellular levels of its associated G-proteins by stimulating their rate of degradation is indicative of an enhanced stoichiometry of coupling of this form of the receptor to G9 and G11.