A Novel Candidate Receptor For The Cardiovascular Responses To Intrathecal Administration Of γ₂-MSH In Anesthetized Rats

Background and purpose:The cardiovascular effects byγ2-melanocyte-stimulating hormone (γ2-MSH) are probably not due to any of the well-known melanocortin subtype receptors. We hypothesize that the sensory neuron-specific receptor (SNSR) may be a candidate receptor for the cardiovascular effects ofγ2-MSH. To test this hypothesis, we investigated the cardiovascular responses to various peptides that have potency for activation of rSNSRl or not.Experimental approach:We examined cardiovascular responses to 1)intrathecal (i.t.) administration ofα-MSH, [Tyr6]-γ2-MSH(6-12),γ2-MSH and BAM(8-22); 2) intravenous (i.v.) pretreatment with theα-adrenoceptor antagonist andβ-adrenoceptor antagonist; 3) intrathecal pretreatment with the novel melanocortin MC3 and MC4 receptor antagonist SHU9119 in male Wistar rats under light urethane anesthesia.Key results:1) [Tyr6]γ2-MSH(6-12),γ2-MSH and bovine adrenal medulla peptides BAM(8-22), administered intrathecally, produced does-response increases in mean arterial pressure (MAP) and indistinctive changes in heart rat (HR). It's worth noting that the does-response curve for the effects of [Tyr6]γ2-MSH(6-12),γ2-MSH and BAM(8-22) on MAP shifted to right in turn, which were consistent with the binding values of these peptides with rSNSRl as determined by Grazzini et al.2) The pressor effects produced as described above by these peptides were blocked by following intravenous (i.v.) administration of a-adrenoceptor antagonist, Phentolamine, but intravenous pretreatment with theβ-adrenoceptor antagonist, Propranolol, had no effect on pressor responses induced by these three peptides.3) MC3/4-R antagonism, did inhibit the cardiovascular effects induced by a-MSH. In contrast, the MAP response induced byγ2-MSH was not significantly modified by MC3/4R antagonism.Conclusion and implication:These results indicate that the cardiovascular effects of [Tyr6]-γ2-MSH(6-12),-γ2-MSHand BAM(8-22) most likely are mediated by rSNSRl. At least that rSNSRl is a novel candidate receptor for the cardiovascular effects ofγ2-MSH.