Synthesis and in vitro Pharmacological Profile of Potent and Selective Peptidic V1a Receptor Agonists.
The neurohypophyseal hormone, 8-arginine-vasopressin (AVP, 1), produces arterial vasoconstriction by activation of the V1a vasopressin receptor (V1aR) located in vascular smooth muscle. This vasopressor effect can be used to treat vasodilatory hypotension in critical care and other conditions . AVP is the endogenous ligand for the V1aR and the two additional vasopressin receptors (V1bR and V2R), and also binds to the oxytocin receptor (OTR). When used as a vasopressor, the lack of selectivity of AVP could possibly generate unwanted side effects such as V2 receptor mediated antidiuresis and release of coagulation factors. In order to find new, more V1a selective agonists, analogs of 1 of the general structure [X2,Ile3,Y4,Z8]VP have been designed, synthesized and tested in vitro.
Results and Discussion
KeywordsVasopressin Receptor Peptide Assembly Diamino Acid Primary Amide Heteroaromatic Ring
he authors wish to thank Marlene Brown and Monica Wolfe for their excellent technical assistance.
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