No / The pro-opiomelanocortin (POMC)-derived peptides, -melanocyte-stimulating hormone, and adrenocorticotropic hormone, are important mediators of human skin pigmentation via action at the melanocortin-1 receptor. Recent data suggests that such a regulatory role also exists for the endogenous opiate, -endorphin (-END). A role for this -END in the regulation of follicular pigmentation, however, has not been determined. This study was designed to examine the involvement of the -END/-opiate receptor system in human follicular melanocyte biology. We employed RT-PCR, and immunohisto/cytochemistry and immunoelectron microscopy using -END and -opiate receptor specific antibodies and a functional role for -END was assessed by direct stimulation with the peptide. This study has demonstrated that human hair follicle melanocytes (HFM) express mRNA for the -opiate receptor and POMC. Furthermore, -END and its high affinity -opiate receptor are expressed at the protein level in glycoprotein100-positive follicular melanocytes and as a function of their anatomic location and differentiation status during the hair growth cycle. Functional studies revealed that -END is a modifier of HFM phenotype via its ability to upregulate melanogenesis, dendricity, and proliferation. These findings suggest a new regulatory role for -END in human HFM biology, providing a new research direction into the fundamental regulation of human hair pigmentation.

Endomorphin 1 (10, 30, 100 nmol/kg) administered intravenously (i.v.) to urethane-anesthetized rats consistently and dose-dependently lowered heart rate (HR) and mean arterial pressure (MAP); the decrease in blood pressure recovered faster as compared to the HR. The effects of endomorphin 2 were qualitatively similar. Naloxone (2 mg/kg, i.v.) completely antagonized the bradycardia and hypotension caused by endomorphin 1. Pretreatment of the rats with atropine methylnitrate, atropine sulfate (2 mg/kg, i.v.) or bilateral vagotomy nearly abolished the bradycardia and attenuated the hypotensive effect of endomorphin 1. Our studies suggest that the bradycardia effect following systemic administration of the new opioid peptide may be explained by activation of vagal afferents and the hypotensive effect may be secondary to a reduction of cardiac output and/or a direct vasodilation.