The cardiac enkephalin, methionine-enkephalin-arginine-phenylalanine (MEAP), alters vagally induced bradycardia when introduced by microdialysis into the sinoatrial (SA) node. The responses to MEAP are bimodal; lower doses enhance bradycardia and higher doses suppress bradycardia. The opposing vagotonic and vagolytic effects are mediated, respectively, by δ1 and δ2 phenotypes of the same receptor. Stimulation of the δ1 receptor reduced the subsequent δ2 responses. Experiments were conducted to test the hypothesis that the δ-receptor interactions were mediated by the monosialosyl ganglioside GM-1. When the mixed agonist MEAP was evaluated after nodal GM-1 treatment, δ1-mediated vagotonic responses were enhanced, and δ2-mediated vagolytic responses were reduced. Prior treatment with the δ1-selective antagonist 7-benzylidenaltrexone (BNTX) failed to prevent attrition of the δ2-vagolytic response or restore it when added afterward. Thus the GM-1-mediated attrition was not mediated by δ1 receptors or increased competition from δ1-mediated vagotonic responses. When GM-1 was omitted, deltorphin produced a similar but less robust loss in the vagolytic response. In contrast, however, to GM-1, the deltorphin-mediated attrition was prevented by pretreatment with BNTX, indicating that the decline in response after deltorphin alone was mediated by δ1 receptors and that GM-1 effectively bypassed the receptor. Whether deltorphin has intrinsic δ1 activity or causes the release of an endogenous δ1-agonist is unclear. When both GM-1 and deltorphin were omitted, the subsequent vagolytic response was more intense. Thus GM-1, deltorphin, and time all interact to modify subsequent δ2-mediated vagolytic responses. The data support the hypothesis that δ1-receptor stimulation may reduce δ2-vagolytic responses by stimulating the GM-1 synthesis.
CB1 receptors modulate the intake of a sweetened-fat diet in response to mu-opioid receptor stimulation of the nucleus accumbens