Proopiomelanocortin-derived peptides and mRNA are expressed in rat heart.

Abstract

Proopiomelanocortin (POMC) is posttranslationally processed to a-MSH, p-endorphin, and a variety of other peptides, not only in the pituitary and brain, but in peripheral tissues as well. P-Endorphin and its immediate precursor p-lipotropin (P-LPH) have recently been identified in cardiac tissue' suggesting that the POMC gene is expressed in heart, although neither the cellular localization nor the posttranslational processing of cardiac POMC peptides has been fully characterized. The localization of p-endorphin, as well as other opioid peptides, in cardiac tissue is consistent with extensive evidence that opiates produce direct effects on cardiac function, reducing cardiac output, coronary pressure, and heart rate.2s3 ACTH, a-MSH, and related ACTH fragments also exhibit potent, albeit opposing, cardioregulatory activities, increasing heart rate and ~ont rac t i l i ty ,~ ,~ although their biosynthesis in cardiac tissue has not, as yet, been demonstrated. In the present study, we further characterized POMC processing in rat heart and also showed, using in situ hybridization, that POMC mRNA is localized within cardiac ventricular muscle cells. Initial gel filtration high-performance liquid chromatography (HPLC) analysis revealed that immunoreactive ACTH and a-MSH are both present in rat heart extracts; however, ACTH levels are quite low relative to a-MSH concentrations (s5%), suggesting that ACTH is almost entirely converted to a-MSH. Reverse phase HPLC further demonstrated that the principal a-MSH-related peptides in heart are a-MSH and N,O-diacetyl-a-MSH; des-acetyl-a-MSH is a relatively minor constituent (FIGURE l). Similarly, sequential gel filtration and cation exchange HPLC analysis indicated that p-LPH is almost entirely converted to p-endorphin and that P-endorphin-1-3 1 is further modified through both N-acetylation and C-terminal proteolysis (FIGURE 1). N-Acetyl-P-endorphin-( 1-31) is the predomi-