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V_1a- and V₂-type vasopressin receptors mediate vasopressin-induced Ca²⁺ responses in isolated rat supraoptic neurones

Laurent Gouzènes, Nancy Sabatier, Philippe Richard, Françoise C. Moos and Govindan Dayanithi

The pharmacological profile of receptors activated by vasopressin (AVP) in freshly dissociated supraoptic magnocellular neurones was investigated using specific V_1a- and V₂-type AVP receptor agonists and antagonists.

In 97 % of AVP-responding neurones (1-3000 nM) V_1a or V₂ receptor type agonists (F-180 and dDAVP, respectively) elicited dose-dependent [Ca²⁺]_i transients that were suppressed by removal of external Ca²⁺.

The [Ca²⁺]_i response induced by 1 µM F-180 or dDAVP was selectively blocked by 10 nM of V_1a and V₂ antagonists (SR 49059 and SR 121463A, respectively). The response to V_1a agonist was maintained in the presence of the V₂ antagonist, and the V₂ agonist-induced response persisted in the presence of the V_1a antagonist.

The [Ca²⁺]_i response induced by 1 µM 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.

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 V₂ types. However, since V₂ 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 V₂ receptor agonist and antagonist act on a 'V₂-like' receptor or a new type of AVP receptor that remains to be elucidated. The possibility that V₂ ligands act on the V_1b receptor cannot be excluded.

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