Cholecystokinin octapeptide increases free intracellular calcium of guinea pig cardiomyocytes through activation of Ca2+ channel and tyrosine kinase.

The aim of the present study was to explore the effect of cholecystokinin octapeptide (CCK-8) on [Ca2+]i and its signal transduction mechanism in isolated guinea pig cardiomyocytes. [Ca2+]i was measured by laser scanning confocal microscopy in single ventricular myocytes which were dissociated by enzymatic dissociation method and loaded with Fluo 3-AM. The changes in [Ca2+]i were represented by fluorescent intensity (F.) or relative fluorescent intensity (Fi/F0%). The results obtained are as follows. (1) In the normal Tyrode's solution containing 1.0 mmol/L Ca2+, CCK-8 (1-104pmol/L) elicited a rapid and marked increase in [Ca2+]i. (2) When cardiomyocytes were pretreated with the Ca2+ chelator EGTA (3 mmol/L) and Ca2+ channel antagonist nisoldipine (0.5 μmol/L) for 5 min, CCK-8 (102 pmol/L) caused a slow and small increase in [Ca2+]i (P 0.01). (3) Pretreatment with the nonselected CCK- receptor (CCK-R) antagonist proglumide (6μmol/L) or the tyrosine kinase inhibitor genistein (1 μmol/L) for 5 min could inhibit the increase of [Ca2+]i induced by CCK-8 (102 pmol/L) (P0.01). The results suggest that CCK-8 increases the [Ca2+]i via activating the receptor-operated Ca2+ channel and eliciting the influx of Ca2+ in isolated guinea pig cardiomyocytes, in which tyrosine kinase may be involved.