Caffeine and ryanodine may act on the plasma membrane of the circular muscle at the flexure region in the guinea-pig colon.
The actions of caffeine and ryanodine on the spontaneous rhythmic activities in the guinea-pig colon were studied by mechanical tension recording. Caffeine reduced the amplitude of the spontaneous rhythmic activity at low concentration (0.3 mM-1 mM). At high concentration (3-10 mM), it induced a phasic transient contraction. The spontaneous rhythmic activity and a phasic contraction induced by caffeine, were blocked by verapamil (3 microM) or by removal of external Ca2+. Ryanodine affected neither resting tension nor frequency of spontaneous activity at 1 microM. However in the circular muscle strips pretreated with ryanodine, a sustained contraction was initiated after the removal of caffeine (10 mM). Continuous Ca2+ influx was necessary for spontaneous rhythmic activities and a phasic transient contraction, because it was abolished completely by the removal of external Ca2+, Verapamil (3 microM), a voltage gated L-type Ca2+ channels blocker, inhibited the spontaneous rhythmic activities and also inhibited phasic transit contraction followed by a sustained contraction induced by 10 mM caffeine. Our results suggest that caffeine may produce a sustained contraction by activating verapamil sensitive Ca2+ channel. In the muscle pretreated with both caffeine and ryanodine, continuous Ca2+ influx may occur also through verapamil sensitive pathway.
Chowdhury
J U
JU
Anatomy 1 Nagoya University School of Medicine, Japan.
Nahar
N S
NS
Torihashi
S
S
D000818:Animals; D002110:Caffeine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D003106:Colon / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D012433:Ryanodine / Q000494:pharmacology*; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D012433:Ryanodine; D002110:Caffeine; D014700:Verapamil; D002118:Calcium