The endothelins (ETs) stimulate the secretion of arginine-vasopressin (AVP) in vivo and in vitro. The activation of hypothalamic ETB 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±17pg·h-1·PP-1 (where PP is posterior pituitary). ETB receptor activation in hypothalamic sites by 1nM IRL1620 dose-dependently increased AVP secretion, with a maximal response of 340±70% of basal·h-1·PP-1, whereas 1nM ET-1, the ETA receptor-selective agonist, inhibited AVP release to 44±8%·h-1·PP-1. Addition of MK801 along with IRL1620 inhibited AVP release to a value no different from basal (122±41%·h-1·PP-1). In contrast, 10µM DNQX [6,7-dinitroquinozaline-2,3-(1H,4H)-dione] did not block ETB receptor-induced AVP release (326±73%·h-1·PP-1), and nor did non-selective α-adrenergic receptor antagonism. The GABAA (where GABA is γ-aminobutyric acid) receptor agonist muscimol (10µM) inhibited AVP release in response to IRL1620 (127±30%·h-1·explant-1). These data suggest that AVP release induced by activation of hypothalamic ETB 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.
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September 2002
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September 01 2002
Modulation of ETB receptor-induced arginine-vasopressin secretion by N-methyl-D-aspartate (NMDA) and γ-aminobutyric acid (GABA)-dependent mechanisms in hypothalamo-neurohypophysial explants
Noreen F. ROSSI;
1Departments of Medicine and Physiology, Wayne State University School of Medicine and John D. Dingell VA Medical Center, 4160 John R #908, Detroit, MI 48201
Dr Noreen F. Rossi (e-mail [email protected]).
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Haiping CHEN
Haiping CHEN
1Departments of Medicine and Physiology, Wayne State University School of Medicine and John D. Dingell VA Medical Center, 4160 John R #908, Detroit, MI 48201
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 162S–166S.
Citation
Noreen F. ROSSI, Haiping CHEN; Modulation of ETB receptor-induced arginine-vasopressin secretion by N-methyl-D-aspartate (NMDA) and γ-aminobutyric acid (GABA)-dependent mechanisms in hypothalamo-neurohypophysial explants. Clin Sci (Lond) 1 September 2002; 103 (s2002): 162S–166S. doi: https://doi.org/10.1042/CS103S162S
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