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.
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
Noreen F
NF
Rossi
Haiping
H
Chen
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)