Antisense mRNA for NPY-Y1 receptor in the medial preoptic area increases prolactin secretion

We investigated the participation of neuropeptide Y-Y1 receptors within the medial preoptic area in luteinizing hormone, follicle-stimulating hormone and prolactin release. Four bilateral microinjections of sense (control) or antisense 18-base oligonucleotides of messenger ribonucleic acid (mRNA) (250 ng) corresponding to the NH2-terminus of the neuropeptide Y1 receptor were performed at 12-h intervals for two days into the medial preoptic area of ovariectomized Wistar rats (N = 16), weighing 180 to 200 g, treated with estrogen (50 µg) and progesterone (25 mg) two days before the experiments between 8.00 and 10:00 a.m. Blockade of Y1 receptor synthesis in the medial preoptic area by the antisense mRNA did not change plasma luteinizing hormone or follicle-stimulating hormone but did increase prolactin from 19.6 ± 5.9 ng/ml in the sense group to 52.9 ± 9.6 ng/ml in the antisense group. The plasma hormones were measured by radioimmunoassay and the values are reported as mean ± SEM. These data suggest that endogenous neuropeptide Y in the medial preoptic area has an inhibitory action on prolactin secretion through Y1 receptors.

Lateral septal area alpha(1)-and alpha(2)-adrenoceptors differently modulate baroreflex activity in unanaesthetized rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Actions of angiotensin II and dopamine in the medial preoptic area on prolactin secretion

Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectornized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of da antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and da actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of da through D-2 receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of da through D, receptors and in other part by inhibition of stimulatory action of da through D2 receptors.

Damage of the medial preoptic area impairs peripheral pilocarpine-induced salivary secretion

The existence of neural connections between the medial preoptic area (MPOA) and the salivary glands and the increase in salivation by thermal or electrical stimulation of the MPOA have suggested an important role of MPOA in the control of salivary gland function. Although direct cholinergic activation of the salivary glands induces salivation, recent studies have suggested that salivation produced by i.p. pilocarpine may also depend on the activation of central mechanisms. Therefore, in the present study, we investigated the effects of bilateral electrolytic lesions of the MPOA on the salivation induced by i.p. pilocarpine. Adult male Holtzman rats (n = 11-12/group) with bilateral sham or electrolytic lesions of the MPOA were used. One, five, and fifteen days after the brain surgery, under ketamine anesthesia, the salivation was induced by i.p. pilocarpine (1 mg/kg of body weight), and saliva was collected using preweighted small cotton balls inserted into the animal's mouth. Pilocarpine-induced salivation was reduced 1 and 5 days after MPOA lesion (341 +/- 41 and 310 +/- 35 mg/7 min, respectively, vs. sham lesions 428 +/- 32 and 495 +/- 36 mg/7 min, respectively), but it was fully recovered at the 15th day post-lesion (561 +/- 49 vs. sham lesion: 618 27 mg/7 min). Lesions of the MPOA did not affect baseline non-stimulated salivary secretion. The results confirm the importance of MPOA in the control of salivation and suggest that its integrity is necessary for the full sialogogue effect of pilocarpine. However, alternative mechanisms probably involving other central nuclei can replace MPOA function in chronically lesioned rats allowing the complete recovery of the effects of pilocarpine. (c) 2006 Published by Elsevier B.V.

Participation of alpha-1 and alpha-2 adrenoceptors of the lateral hypothalamic area in water intake, and renal sodium, potassium and urinary Volume excretion induced by central administration of angiotensin II

The circumventricular structures and the lateral hypothalamus (LH) have been shown to be important for the central action of angiotensin II (ANGII) on water and electrolyte regulation. Several anatomical findings have demonstrated neural connection between circumventricular structures and the LH, the present experiments were conducted to investigate the role of the alpha-adrenergic antagonists and agonistic injected into the LH on the water intake, sodium and potassium excretion elicited by injections of ANGII into the lateral ventricle (LV), the water intake was measured every 30 min over a period of 120 min. The sodium, potassium and urinary volume were measured over a period of 120 min in water-loaded rats. The injection of ANGII into the LV increased the water intake, which was reduced by previous injection of clonidine (an alpha-2-adrenergic agonist) into the LH. The injection of yohimbine (an alpha-2-adrenergic antagonist) and prazosin (an alpha-l-adrenergic antagonist) into the LH, which was done before injecting ANGII into the LV, also reduced the water intake induced by ANGII. The injection of ANGII into the LV reduced the sodium, potassium and urinary volume. Previous treatment with clonidine attenuated the action of ANGII in reducing the sodium, potassium and urinary volume, whereas previous treatment with yohimbine attenuated the effects of ANGII but with less intensity than that caused by clonidine. Previous treatment with prazosin increased the inhibitory effects of ANGII in those parameters. The injection of yohimbine and prazosin, which was done before the injection of clonidine, attenuated the effect of clonidine on the ANGII mechanism. The results of this study led us to postulate that when alpha-2-adrenergic receptors are blocked, the clonidine may act on the imidazoline receptors to produce its effects on the ANGII mechanism. We may also conclude that the LH is involved with circumventricular structures, which present excitatory and inhibitory mechanisms. Such mechanisms are responsible for regulating the renal excretion of sodium, potassium and water, (C) 2000 Elsevier B.V.

Effects of V-1 and angiotensin receptor subtypes of the paraventricular nucleus on the water intake induced by vasopressin injected into the lateral septal area

In this study, we investigated the influence of d(CH2)(5)-Tyr (Me)-AVP (AAVP) an antagonist of V-1 receptors of arginine(8)-vasopressin (AVP) and the effects of losartan and CGP42112A (selective ligands of the AT, and AT, angiotensin receptors, respectively) injections into the paraventricular nucleus (PVN) on the thirst effects of AVP stimulation of the lateral septal area (LSA). AVP injection into the LSA increased the water intake in a dose-dependent manner. AAVP injected into the PVN produced a dose-dependent reduction of the drinking responses elicited by LSA administration of AVP. Both the AT(1) and AT(2) ligands administered into the PVN elicited a concentration-dependent inhibition in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A the increase in the AVP response. These results indicate that LSA dipsogenic effects induced by AVP are mediated primarily by PVN AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple angiotensin II (ANG II) receptor subtypes. These results also suggests that facilitatory effects of AVP on water intake into the LSA are mediated through the activation of V-receptors and that the inhibitory effect requires V-receptors. Based on the present findings, we suggest that the administration of AVP into the LSA may play a role in the PVN control of water control. (C) 2003 Elsevier B.V. All rights reserved.

Effects of angiotensin and vasopressin V-1 receptors on water and sodium intake induced by injection of vasopressin into lateral septal area

The specific arginine(8)-vasopressin (AVP) V, receptors antagonist (AAVP) was injected (20, 40 and 80 nmol) into the lateral septal area (LSA) to determine the effects of selective septal V, receptor on water and 3% sodium intake in rats. Was also observed the effects of losartan and CGP42112A (select ligands of the AT(1) and AT(2) ANG II receptors, respectively) injected into LSA prior AVP on the same appetites. Twenty-four hours before the experiments, the rats were deprived of water. The volume of drug solution injected was 0.5 mul. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2,0 h. Injection of AVP reduced the water and sodium ingestion vs. control (0.15 M saline). Pre-treatment with AAVP (40, 80 and 160 nmol) did not alter the decrease in the water ingestion induced by AVP, whereas AAVP abolished the action of AVP-induced sodium intake. Losartan (40, 80 and 160 nmol) did not alter the effect of AVP on water and sodium intake, whereas CGP42112A (20, 40 and 60 nmol) at the first 30 min increased water ingestion. Losartan and CGP42112A together increased the actions of AVP, showing more pronounced effects than when the two antagonists were injected alone. The results showed that AVP inhibited the appetites and these effects were increased by the AAVP. The involvement of angiotensinergic receptors in the effects of AVP is also suggested. (C) 2004 Elsevier B.V. All rights reserved.

Role of serotonergic 5-HT1A and oxytocinergic receptors of the lateral septal area in sodium intake regulation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

On a possible dual role for the lateral septal area 5-HT1A receptor system in the regulation of water intake and urinary excretion

The 5-hydroxytryptamine (5-HT)(1A) receptor system plays a prominent role in a variety of physiological functions and behavior and regulation of this responsiveness of the receptor system has been implicated in the central regulation of water intake and urinary excretion. The lateral septal area (LSA) exhibits a high density of 5-HT1A receptors, as well as a subpopulation of oxytocin (OT) receptors. Here we report the effects of pMPPF (a selective 5-HT1A antagonist), d(CH2)(5)[Tyr(Me)(2)Thr(4), Orn(5), Tyr(NH2)(9)]-vasotocin (an OT antagonist), and that 5-HT1A receptor system is regulated as a consequence of activation of the Na+ channel by veratridine. Cannulae were implanted into the LSA of rats to enable the introduction of the drugs. Injections of 8-OH-DPAT (a 5-HT1A agonist) blocked water intake and increased urinary excretion, while pMPPF or the OT antagonist injected bilaterally before 8-OH-DPAT blocked its inhibitory effect on water intake and its diuretic effect. In contrast, increases in extracellular sodium levels induced by the sodium channel modulator, veratridine, enhanced 5-HT1A responsiveness for water intake and reduced the diuretic effects induced by 8-OH-DPAT. These trials demonstrated that the responsiveness of the 5-HT1A receptor system in the LSA can be enhanced or depressed as a consequence of an induced rise in extracellular sodium. (C) 2010 Elsevier B.V. All rights reserved.

Involvement of the intermediate nucleus of the lateral septal area on angiotensin II-induced dipsogenic and pressor responses

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

Influence of arginine vasopressin receptors and angiotensin receptor subtypes on the water intake and arterial blood pressure induced by vasopressin injected into the lateral septal area of the rat

In this study we investigated the influence of d(CH2)(5)-Tyr(Me)-[Arg(8)]vasopressin (AAVP) and [adamanteanacetyl(1),0-ET-DTyr(2), Val(4), aminobutyryl(6), Arg(8,9)]-[Arg(8)]vasopressin (ATAVP), which are antagonists of vasopressin V-1 and V-2 receptors, and the effects of losartan, a selective angiotensin AT(1) receptor antagonist, and CGP42112A, a selective AT(2) receptor antagonist, injected into the lateral septal area (LSA) on thirst and hypertension induced by [Arg(8)]vasopressin (AVP). AAVP and ATAVP injected into the LSA reduced the drinking responses elicited by injecting AVP into the LSA. Both the AT(1) and AT(2) ligands administered into the LSA elicited a concentration-dependent decrease in the water intake induced by AVP injected into the LSA, but losartan was more effective than CGP42112A. The increase in MAP, due to injection of AVP into the LSA, was reduced by prior injection of AAVP from 18 +/- 1 to 6 +/- 1 mm Hg. Losartan injected into the LSA prior to AVP reduced the increase in MAP to 7 +/- 0.8 mm Hg. ATAVP and CGP42112A produced no changes in the pressor effect of AVP. These results suggest that the dipsogenic effects induced by injecting AVP into the LSA were mediated primarily by AT(1) receptors. However, doses of losartan were more effective when combined with CGP42112A than when given alone, suggesting that the thirst induced by AVP injections into LSA may involve activation of multiple AVP and angiotensin II receptor subtypes. The pressor response of AVP was reduced by losartan and by AAVP. CGP42112A and ATAVP did not change the AVP pressor response. These results suggest that facilitator effects of AVP on water intake are mediated through the activation of V-1 receptors and that the inhibitory effect requires V-2 receptors. The involvement of AT(1) and AT(2) receptors can be postulated. Based on the present findings, we suggest that the AVP in the LSA may play a role in the control of water and arterial blood pressure balance. (C) 2004 Elsevier B.V. All rights reserved.

Ventromedial hypothalamus lesions increase the dipsogenic responses and reduce the pressor responses to median preoptic area activation

In this study, we investigated the participation of adrenergic receptors of the median preoptic area (MnPO) and the participation of ventromedial hypothalamus (VMH) in angiotensin II- (ANG II)-induced water intake and presser responses. Male rats with sham or electrolytic VMH lesions and a stainless steel cannula implanted into the MnPO were used. Noradrenaline, clonidine (an alpha(2)-adrenergic receptor agonist), or phenylephrine (an alpha(1)-adrenergic receptor agonist) injected into the MnPO of sham-lesioned rats reduced water ingestion induced by ANG II injected into the same area. In VMH-lesioned rats ANG II-induced water intake increased with a previous injection of noradrenaline, phenylephrine, or isoproterenol. The presser response induced by ANG II injected into the MnPO was reduced in VMH-lesioned rats, whereas the presser response induced by clonidine was abolished. Previous treatment with noradrenaline and phenylephrine into the MnPO of sham-lesioned rats produced a presser response, and a hypotensive response was obtained with the previous administration of noradrenaline, phenylephrine or isoproterenol into the MnPO of VMH-lesioned rats. These results show that VMH is essential for the dipsogenic and presser responses induced by adrenergic and angiotensinergic activation of the MnPO in rats. (C) 1997 Elsevier B.V.

ROLE OF ADRENERGIC PATHWAYS OF THE MEDIAL PREOPTIC AREA IN ANGII-INDUCED WATER-INTAKE AND RENAL EXCRETION IN RATS

In this study, we investigated the participation of adrenergic neurotransmission in angiotensin II- (ANGII)-induced water intake and urinary electrolyte excretion by means of injection of the alpha(1)-, alpha(2)-, and beta-adrenoceptor antagonists and ANGII into the medial preoptic area (MPOA) in rats. Prazosin (an alpha(1)-adrenergic antagonist) antagonized the water ingestion, Na+, K+ and urine excretion induced by ANGII, whereas yohimbine (an alpha(2)-adrenergic antagonist) enhanced the Na+, K+ and urine excretion induced by ANGII. Propranolol (a nonselective beta-adrenoceptor blocker) antagonized the water ingestion and enhanced the Na+ and urine excretion induced by ANGII. Previous treatment with prazosin reduced the presser responses to ANGII, whereas yohimbine had opposite effects. Previous injection of propranolol produced no effects in the presser responses to ANGII. These results suggest that the adrenergic neurotransmission in the MPOA may actively participate in ANGII-induced dipsogenesis, natriuresis, kaliuresis and diuresis in a process that involves alpha(1)-, alpha(2)-, and beta-adrenoceptors.