Modulation of ET(B) receptor-induced arginine-vasopressin secretion by N-methyl-D-aspartate (NMDA) and gamma-aminobutyric acid (GABA)-dependent mechanisms in hypothalamo-neurohypophysial explants.
The endothelins (ETs) stimulate the secretion of arginine-vasopressin (AVP) in vivo and in vitro. The activation of hypothalamic ET(B) receptors increases AVP release, but the neurotransmitters mediating these responses are not known. In the compartmentalized hypothalamo-neurohypophysial explant model, the overall basal release of AVP was 53+/-17 pg x h(-1) x PP(-1) (where PP is posterior pituitary). ET(B) receptor activation in hypothalamic sites by 1 nM IRL1620 dose-dependently increased AVP secretion, with a maximal response of 340+/-70% of basal x h(-1) x PP(-1), whereas 1 nM ET-1, the ET(A) receptor-selective agonist, inhibited AVP release to 44+/-8% x h(-1) x PP(-1). Addition of MK801 along with IRL1620 inhibited AVP release to a value no different from basal (122+/-41% x h(-1) x PP(-1)). In contrast, 10 microM DNQX [6,7-dinitroquinozaline-2,3-(1H,4H)-dione] did not block ET(B) receptor-induced AVP release (326+/-73% x h(-1) x PP(-1)), and nor did non-selective alpha-adrenergic receptor antagonism. The GABA(A) (where GABA is gamma-aminobutyric acid) receptor agonist muscimol (10 microM) inhibited AVP release in response to IRL1620 (127+/-30% x h(-1) x explant(-1)). These data suggest that AVP release induced by activation of hypothalamic ET(B) receptors is mediated by a hypothalamic N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. In turn, the local release of GABA associated with NMDA activation may exert an inhibitory influence and dampen the AVP secretory response.
Rossi
Noreen F
NF
Department of Medicine, Wayne State University School of Medicine and John D. Dingell VA Medical Center, 4160 John R #908, Detroit, MI 48201, USA. nrossi@intmed.wayne.edu
Chen
Haiping
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000378:metabolism*; D018079:Receptors, GABA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012636:Secretory Rate / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011810:Quinoxalines; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D010643:Phenoxybenzamine; D001127:Arginine Vasopressin; C074308:sovateltide; C077420:Cys(11)-Cys(15)-endothelin-1 (11-21); D009118:Muscimol; C056723:FG 9041; D016291:Dizocilpine Maleate; C072247:cyclo(Trp-Asp-Pro-Val-Leu)