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 Ca(2+) and its signal transduction mechanism in isolated guinea pig cardiomyocytes. Ca(2+) 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 Ca(2+) were represented by fluorescent intensity (F(i)) or relative fluorescent intensity (F(i)/F(O)%). The results obtained are as follows. (1) In the normal Tyrode's solution containing 1.0 mmol/ L Ca(2+), CCK-8 (1-10(4) pmol/L) elicited a rapid and marked increase in Ca(2+). (2) When cardiomyocytes were pretreated with the Ca(2+) chelator EGTA (3 mmol/L) and Ca(2+) channel antagonist nisoldipine (0.5 micromol/L) for 5 min, CCK-8 (10(2)pmol/L) caused a slow and small increase in Ca(2+) (p< 0.01). (3) Pretreatment with the nonselected CCK- receptor (CCK-R) antagonist proglumide (6 micromol/L) or the tyrosine kinase inhibitor genistein (1 micromol/L) for 5 min could inhibit the increase of Ca(2+) induced by CCK-8 (10(2) pmol/L) (p<0.01). The results suggest that CCK-8 increases the Ca(2+) via activating the receptor-operated Ca(2+) channel and eliciting the influx of Ca(2+) in isolated guinea pig cardiomyocytes, in which tyrosine kinase may be involved.