Effects of swimming and nandrolone decanoate treatment on vas deferens response to norepinephrine

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Boron transport in Eucalyptus. 2. Identification in silico of a putative boron transporter for xylem loading in eucalypt

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Transporter protein genes are differentially expressed in Acidithiobacillus ferrooxidans LR maintained in contact with covellite

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Functional Characterization of an Aspergillus fumigatus Calcium Transporter (PmcA) that Is Essential for Fungal Infection

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

INVOLVEMENT OF SWIMMING-INDUCED ACUTE STRESS IN THE SENSITIVITY OF RAT VAS-DEFERENS TO NOREPINEPHRINE

1. The effects of swimming-induced stress on rat sensitivity to norepinephrine were studied.2. Through microscopic analysis of the stomach from swimming stressed rats significant ulceration was observed, confirming that the stress situation was really present.3. Sensitivity to norepinephrine either in the presence or in the absence of cocaine and propranolol in acutely swimming stressed rats was not altered significantly.4. Bilateral adrenalectomy was performed in rats 2 days before swimming and acute stress resulted in a supersensitivity to norepinephrine, indicating that adrenal glands may, at least, partially mediate the sensitivity to this drug in vasa deferentia isolated from these animals.

Acute swimming stress induces changes in noradrenergic mechanisms in order to maintain the response pattern of the rat vas deferens to norepinephrine

This study investigated mechanisms involved in the maintenance of the functional response pattern of the postjunctional alpha(1)-adrenoceptor in vas deferens isolated from rats submitted to acute swimming stress. The plasma corticosterone levels increased approximately three times after the swimming stress in the nontreated rats as well as after swimming stress in the rats pretreated with desipramine (DMI), yohimbine (YO), or DMI with YO. No alteration was detected in the sensitivity to norepinephrine (NE) in the vasa deferentia from the stressed rats or stressed rats treated with DMI or DMI with YO, in relation to their respective control. However, when the vasa deferentia were previously incubated with DMI, a reduction in sensitivity to NE in organs from stressed rats was observed. Vasa deferentia excised from rats pretreated with YO before the swimming stress showed an increase in postjunctional alpha(1)-response that was abolished by prazosin (PZ). Thus, the neuronal uptake, the prejunctional alpha(2)-adrenoceptors (mediating prejunctional inhibition), the occupancy and functional response of the postjunctional alpha(1)-adrenoceptors, and the emotional stress component were very important for the determination of the noradrenergic response pattern in vas deferens from rats submitted to acute swimming stress. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

NtWBC1, an ABC transporter gene specifically expressed in tobacco reproductive organs

To identify genes specifically or predominantly expressed in the stigmas/styles and to establish their possible function in the reproductive process of plants, a tobacco stigma/style cDNA library was constructed and differentially screened, resulting in the isolation of several cDNA clones. The molecular characterization of one of these clones is described here. After sequencing the cDNA and the isolated genomic clone, it was determined that the corresponding gene encodes a protein containing an ATP-binding cassette, characteristic of ABC transporters. This gene, designated as NtWBC1 (Nicotiana tabacum ABC transporter of the White-Brown Complex subfamily), encodes a protein that contains the typical structure of the 'half-transporters' of the White subfamily. To establish the spatial expression pattern of the NtWBC1 gene, northern blot and real-time RT-PCR analyses with total RNA from roots, stems, leaves, sepals, petals, stamens, stigmas/styles, ovaries, and seeds were performed. The result revealed a transcript of 2.5 kb present at high levels in stigmas and styles and a smaller transcript (2.3 kb) present at a lower level in stamens. NtWBC1 expression is developmentally regulated in stigmas/styles, with mRNA accumulation increasing toward anthesis. In situ hybridization experiments demonstrated that NtWBC1 is expressed in the stigmatic secretory zone and in anthers, at the stomium region and at the vascular bundle. NtWBC1 is the first ABC transporter gene with specific expression in plant reproductive organs to be identified and its expression pattern suggests important role(s) in the reproductive process.

Cognitive and olfactory deficits in Machado-Joseph disease: A dopamine transporter study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Study of the contraction induced by norepinephrine and clonidine in the isolated guinea-pig ileum

Norepinephrine (NE) and clonidine produce a phasic, dose-dependent contraction of the isolated guinea-pig terminal ileum. The effect of NE was blocked by prazosin which produced a parallel rightward shift of the concentration-effect curve to NE, with a significant depression of maximum effects. Yohimbine and indomethacin noncompetitively blocked, whereas practolol potentiated, the contractile effect of NE. The contractile effect of clonidine was not antagonized by indomethacin or atropine. These results suggest that the isolated guinea-pig terminal ileum has excitatory receptors sensitive to clonidine stimulation and excitatory alpha receptors sensitive to blockade by prazosin, and that the activation of the latter may be related to the activation of endogenous prostaglandin synthesis.

Role of androgenic deprivation on the contractile response to norepinephrine in vas deferens isolated from rats submitted to swimming-stress

The effects of androgenic deprivation induced by castration on the norepinephrine contractile response of vas deferens from rats, which have been submitted to acute swimming-stress were determined. Acute swimming-stress led to subsensitivity to norepinephrine in vas deferens excised from intact rats. Similarly, castration also induced subsensitivity to norepinephrine, but no further subsensitivity occurred in organs from castrated rats submitted to acute stress. The results indicate a different response to norepinephrine in terms of relative responsiveness ratio, when vas deferens was excised from castrated rats or castrated rats submitted to acute stress. It is suggested that androgenic steroids modulate the recovery of homeostasis in rat vas deferens during acute stress, and that this effect may involve mechanisms that affect both the sensitivity of adrenergic receptors and the system of neuronal uptake of catecholamines.

Changes in norepinephrine and epinephrine concentrations in adrenal gland of the rats submitted to acute immobilization stress

Catecholamines act as neurotransmitters and hormones. Studies conducted to understand the synthesis and metabolism of these monoamines during stress have been the main concern of many authors. This work proposes to investigate the time course of changes in epinephrine and norepinephrine concentration in adrenal gland obtained from rats submitted to acute immobilization stress. The results of the present study indicate that acute immobilization stress during 5 and 15min did not provoke changes in epinephrine and norepinephrine concentrations in adrenal gland in relation to the control group. Such results are justified due to the short time of the stress, showing that the stress did not provoke physiological alteration. The epinephrine and norepinephrine concentrations in adrenal gland increased significantly after the immobilization session in stressed groups during 30 and 50min as compared to control group. This increase probably is due to the emotional component of the immobilization stress. In this way, we suggested that the immobilization stress provoke increase in the biosynthesis of catecholamines in the adrenal gland from rats. However, the results shows that a maximum increase is reached at 30min of immobilization stress and then a decrement of catecholamines levels starts at 50min of the experimental design. This decline in catecholamines level may be consequence of adaptation to stress situations, an increase of the activity of the uptake systems and/or metabolization of catecholamines. In conclusion, these results suggest an effective participation of the adrenal glands to maintain the homeostasis of organism to the stressful conditions. © 2003 Elsevier Ltd. All rights reserved.

Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that a1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the a1B and a1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent a1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that thisproperty of OXY is not limited to recombinant receptors expressed in cell systems. The results of the present study are clearly indicative of agonist-directed a1A-AR regulation. OXY shows functional selectivity relative to NE and PE at a1A-ARs, leading to significant receptor desensitization and internalization, which is important in view of the therapeutic vasoconstrictor effects of this drug and the varied biologic process regulated by α1A-ARs. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.

Nitensidine A, a guanidine alkaloid from Pterogyne nitens, is a novel substrate for human ABC transporter ABCB1

The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity. © 2013 Elsevier GmbH. All rights reserved.