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Piperine, a major pungent agent of black peppers, induced both positive chronotropic and inotropic responses in the isolated atria of rats. These responses were not blocked by various antagonists but exhibited rapid tachyphylaxis. After exposure to piperine in vitro, endogenous calcitonin gene-related peptide (CGRP) was profoundly depleted from intracardiac nerves. These results suggest that piperine releases endogenous CGRP from intracardiac non-adrenergic non-cholinergic nerves and that released CGRP exerts positive chronotropic and inotropic effects.
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