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 antagoni...
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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.
SUMMARYAnalogues of oxytocin and deaminooxytocin with 4‐glutamine replaced by 4‐glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much l...
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SUMMARYAnalogues of oxytocin and deaminooxytocin with 4‐glutamine replaced by 4‐glutamic acid methyl ester readily lose their uterotonic activity when incubated with rat serum, presumably by hydrolysis to the much less active 4‐glutamic acid derivatives. On the other hand, inactivation of the deaminooxytocin analogue in the rat uterus, as demonstrated by the ‘oil‐bath’technique, is only slightly more rapid than that of deaminooxytocin and distinctly slower than that of oxytocin. Itsin situ/in vitroratio of uterotonic activity is less than 0.1 whereas that for deaminooxytocin is about 3 and also the persistence of the uterotonic effectin situis slightly less than that of deaminooxytocin. The results with these ‘rapidly inactivated’analogues can be used as proof of some predictions of the three‐compartment model for tissue distribution of neurohypophysial hormones and its influence upon the time course of a biological response published earlier. The potential use of analogues of neurohypophysial hormones as probes for inactivation mechanisms and the results thus far obtai
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