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.

This content is only available as a PDF.
You do not currently have access to this content.