An Endogenous Purified Peptide Modulates Ca2+ Channels in Neurons and Cardiac Myocytes
Transport of Ca2+ through membrane channels plays an important role in excitation-contraction coupling of cardiac and smooth muscle, in neurosecretion, and in neuronal signaling. The discovery that dihydropyridines can regulate voltage-activated Ca2+ channels (Fleckenstein et al. 1972) set the stage for studies on the structure and function of these channels and provided a biochemical probe useful in the search for possible endogenous modulators (EMs). Studies on the existence of endogenous Ca2+ -channel modulators were triggered by various reports providing electrophysiological and pharmacological evidence for the involvement of organic Ca2+ -channel antagonists in Ca2+ -channel regulation (Fleckenstein 1977; Janis and Diamond 1981; Tsien 1984). Supporting the idea of the possible existence of EMs were reports showing that sympathetic denervation of the heart up-regulated the dihydropyridine binding sites in this tissue (Skattebol1986) and that up-regulation of 3H-nitrendipine binding sites occurred in mouse brain after chronic treatment with morphine (Ramkumar and El-Fakahany1984). Janis et al. (1988) have reported that a number of endogenous substances alter Ca2+ -channel activity by either inhibiting 3H-dihydropyridine binding or modifying potential-dependent Ca2+ currents. For example, dynorphine A inhibited Ca2+ -channel activity, while calcitoninlike peptides enhanced the Ca2+ channel without altering 3H-dihydropyridine binding (Nohmi et al. 1985; Tsunoo et al. 1986; MacDonald and Merz 1987).
KeywordsEndogenous Ligand Cerebellar Granule Cell None None Palmitoyl Carnitine Endogenous Modulator
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