Sympathetic noradrenergic fibers as the source of immunoreactive alpha-neoendorphin and dynorphin in the guinea pig heart.

Dynorphin and alpha-neoendorphin bind to the kappa subtype of opioid receptors and have been shown to inhibit the release of noradrenaline from cardiac sympathetic axons. The purpose of this study was to elucidate the endogenous localization of dynorphin and alpha-neoendorphin in the guinea pig heart. This goal was achieved by double- and triple-labelling immunofluorescence. Dynorphin- and alpha-neoendorphin-immunoreactive nerve fibers were numerous around coronary blood vessels and among cardiomyocytes. They also contained immunoreactivities to the rate-limiting enzyme of catecholamine synthesis tyrosine hydroxylase and to neuropeptide Y. These fibers disappeared in response to chemical sympathectomy (6-hydroxydopamine treatment). In contrast, substance P/calcitonin gene-related peptide-immunoreactive axons of sensory origin did not contain dynorphin and alpha-neoendorphin immunoreactivities and were unaffected by chemical sympathectomy. The findings demonstrate that immunoreactive dynorphin and alpha-neoendorphin are contained in postganglionic sympathetic nerve fibers innervating coronary blood vessels and cardiac muscle. Therefore, the inhibitory effect of these peptides upon noradrenaline release from the sympathetic terminal may well be an autoinhibitory feedback loop.