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+)](i) and its signal transduction mechanism in isolated guinea pig cardiomyocytes. [Ca(2+)](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 [Ca(2+)](i) 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+)](i). (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+)](i) (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+)](i) induced by CCK-8 (10(2) pmol/L) (p<0.01). The results suggest that CCK-8 increases the [Ca(2+)](i) 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.
Zhao
Xiao-Yun
XY
Hebei Provincial Geriatric Key Laboratory, Shijiazhuang 050051, China.
Ling
Yi-Ling
YL
Shang
Zhong-Lin
ZL
Li
Qing
Q
Yin
Jing-Xiang
JX
Tan
Guo-Jun
GJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D002469:Cell Separation; D006168:Guinea Pigs; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D015737:Nisoldipine / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D012844:Sincalide / Q000494:pharmacology*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D015737:Nisoldipine; D011505:Protein-Tyrosine Kinases; D012844:Sincalide; D002118:Calcium