V1a- and V2-type vasopressin receptors mediate vasopressin-induced Ca2+ responses in isolated rat supraoptic neurones

1. The pharmacological profile of receptors activated by vasopressin (AVP) in freshly dissociated supraoptic magnocellular neurones mas investigated using specific V-1a- nnd V-2-type AVP receptor agonists and antagonists. 2. In 97% of AVP-responding neurones (1-3000 nM) V-1a or V-2 receptor type agonists (F-180 and dDAVP, respectively) elicited dose-dependent [Ca2+](i) transients that were suppressed by removal of external Ca2+. 3. The [Ca2+](i) response induced by 1 mu M F-180 or dDAVP JP was selectively blocked by 10 nM of V-1a and V-2 antagonists (SR 49059 and SR 121463A, respectively). The response to V-1a agonist was maintained in the presence of the V-2 antagonist, and the V-2 agonist-induced response persisted in the presence of the V-1a antagonist. 4. The [Ca2+](i) response induced by 1 mu M AVP was partially (61%) blocked by 10 nM SR 121463A. This blockade was increased by a further 31% with the addition, of 10 nM SR 49059. Similarly, the AVP-induced response was partially (47%) decreased by SR 49059, and a further inhibition of 33% was achieved in the presence of SR 121463A. 5. We demonstrate that AVP acts: on the magnocellular neurones via two distinct types of AVP receptors that exhibit the pharmacological profiles of V-1a and V-2 types. However, since V-2 receptor mRNA is not expressed in the supraoptic nucleus (SON), and since V-1b receptor transcripts are observed in the SON, we propose that the V-2 receptor agonist and antagonist act on a 'V-2-like' receptor or a new type of AVP receptor that remains to be elucidated. The possibility that V-2 ligands act on the V-1b receptor cannot be excluded.