Kappa Agonists and Vasopressin Secretion

Abstract

The effects of opiates on vasopressin secretion have been controversial for many years. This is probably due to the existence of different types of opioid receptors and to the lack of specificity of the compounds used. Specific ĸ agonists, which have been described recently, produce a marked diuretic effect without any associated increase in electrolyte elimination. They seem to exert their effects through an interaction with ĸ receptors situated on nerve terminals and/or pituicytes. These receptors could be directly coupled to L-type calcium channels, their activation leading to a decrease in the effectiveness of action potentials to evoke vasopressin secretion from nerve terminals in the neurohypophysis. This mechanism of action may explain the decrease in plasma vasopressin levels induced by ĸ agonists.

Kappa-opioid receptors and relapse-like drinking in long-term ethanol-experienced rats

“…Like other κ-opioid receptor agonists, CI-977 does induce diuresis (Hunter et al 1990). The diuresis induced by κ-opioid receptor agonists is characterised by a selective increase of water elimination without any associated increase in electrolyte elimination, which is due to an inhibition of vasopressin release and a direct effect on renal function (Dykstra et al 1987;Leander et al 1987;Hamon and Jouquey 1990). It can not be excluded that the diuretic action contributed to the increased ethanol intake.…”

Hyponatremia in cirrhosis: From pathogenesis to treatment

“…117 -Opioid receptors are present in the supraoptic nuclei and in the neurohypophysis, 118 and there is evidence that -opioid agonists reduce VP release by diminishing the effectiveness of action potentials to evoke its secretion from nerve terminals. 119 The feasibility of the second option (i.e., to block the V 2 receptor) has been demonstrated by several compounds that promote aquaresis in experimental animals. [120][121][122][123] The third therapeutical strategy is represented by demeclocycline, which was the first inhibitor of the renal effect of VP used in humans.…”

Sustained aquaretic effect of the V2‐AVP receptor antagonist, RWJ‐351647, in cirrhotic rats with ascites and water retention

“…Two families of agents, which are able to inhibit AVP activity and possess aquaretic effects, have emerged. The first type consists in the κ ‐opioid receptor agonists, which increase urine volume (UV) and decrease urinary osmolality in humans and experimental animals mainly by inhibiting AVP release ( Slizgi & Ludens, 1982 ; Hamon & Jouquey, 1990 ). However, κ ‐opioid agonists are of limited value because they may display some adverse effects, which are probably related to their central mechanism of action ( Bellisant et al ., 1996 ).…”