The source of calcium for CCK-induced contraction of the guinea-pig gall bladder.
The sources of calcium for cholecystokinin octapeptide (CCK-OP)-induced gallbladder smooth muscle contraction are considered both extracellular and intracellular, but the relative need for intracellular calcium especially at low, physiological concentrations is not clear. To better define the calcium sources responsible for guinea-pig gallbladder contractions in vitro, we inhibited calcium influx using the calcium channel blocker, methoxyverapamil, and a calcium-free Krebs' solution. Availability and release of intracellular calcium stores were depleted by strontium substitution and ryanodine. CCK-OP was compared to bethanechol and potassium chloride (KCl). Preventing calcium influx with 10(-5) M methoxyverapamil depressed the responses to CCK-OP, bethanechol and KCl. Methoxyverapamil, however, had little effect on the time-dependent generation of tension to CCK-OP, but significantly reduced the response to bethanechol and KCl, each at ED50. The duration of the contractile response in the calcium-free Krebs' solution to CCK-OP was longer than that for bethanechol. Strontium (2.5 mM) significantly attenuated the response to CCK-OP and bethanechol, but not to KCl. Ryanodine significantly reduced contractions induced by CCK-OP but not for bethanechol, both at low dose ED25. These results indicate that contraction of the guinea-pig gallbladder induced by CCK-OP, bethanechol and KCl requires extracellular calcium influx. Further, the initiation and maintenance of contraction by CCK-OP and bethanechol necessitates calcium mobilisation from intracellular stores. CCK-OP may have a greater penchant for these calcium stores, particularly at physiological doses.
GI Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.
E A
EA
Shaffer
A
A
Bomzon
H
H
Lax
J S
JS
Davison
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D005704:Gallbladder / Q000502:physiology*; D005711:Gallopamil / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D012433:Ryanodine / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology*; D013324:Strontium / Q000494:pharmacology
D001626:Bethanechol Compounds; D018723:Bethanechol; D012433:Ryanodine; D005711:Gallopamil; D011189:Potassium Chloride; D012844:Sincalide; D002118:Calcium; D013324:Strontium