Vasopressin release from the rat hypothalamo-neurohypophysial system: effects of tachykinin NK-1 and NK-2 receptors agonists and antagonists.

OBJECTIVES: Present experiments were undertaken to study the influence of peptide NK-1 and NK-2 receptor agonists and antagonists as well as substance P and neurokinin A (the natural ligands for these tachykinin receptors) on vasopressin (AVP) secretion from the rat hypothalamo-neurohypophysial (HN) system in vitro.

RESULTS: The results showed that both substance P and highly selective tachykinin NK-1 receptor agonist, i.e., [Sar9,Met(O2)11]-Substance P, enhanced significantly AVP secretion, while the NK-1 receptor antagonist (Tyr6,D-Phe7,D-His9)-Substance P (6-11)--sendide--was found to antagonize the substance P-induced hormone release from isolated rat HN system (all peptides at the concentration of 10(-7) M/L). The NK-2 receptor selective agonist (beta-Ala8)-Neurokinin A (4-10) was essentially inactive in modifying AVP release from the rat HN system in vitro, while neurokinin A (the natural ligand for this tachykinin receptor) was found to stimulate the AVP release; this effect of neurokinin A has been diminished by the NK-2 receptor antagonist (Tyr5,D-Trp(6,8,9),Lys-NH2(10))-Neurokinin A (4-10).

CONCLUSION: The present data indicate a role for tachykinin NK-1 (and possibly for NK-2) receptors in tachykinin-mediated stimulation of AVP secretion from the rat HN system in vitro.