Sustained contraction produced by caffeine after ryanodine treatment in the circular muscle of the guinea‐pig gastric antrum and rabbit portal vein

Abstract

Japan 1 Caffeine inhibited spontaneous mechanical activity at 0.3-1 mM, but produced a tonic contraction at concentrations higher than 3 mM in the circular muscle of the guinea-pig gastric antrum. In the circular muscle of the rabbit portal vein, caffeine at concentrations higher than 1 mM produced an early phasic contraction followed by a small tonic component. The caffeine-induced contraction was abolished by removal of the external Ca2" more rapidly in the gastric antrum than the portal vein.2 When the preparations were pretreated with ryanodine (1 gM) a sustained contraction developed on wash-out of caffeine (10 mM) both in the gastric antrum and portal vein. This contraction was not affected by nicardipine (3 gxM) or verapamil (3 gM), but was readily abolished by removal of the external Ca2+ or by addition of cobalt (1 mM). Spontaneous electrical activity, the slow wave, in gastric muscles was blocked in the presence of 10 mm caffeine, but reappeared during the sustained contraction. 3 Both the contractions induced directly by caffeine and those produced following caffeine wash-out after ryanodine treatment were accompanied by a maintained increase in intracellular Ca2+ concentration measured with fura-2. 4 The presence or absence of Ca2" during the application of ryanodine did not affect the ability of caffeine to initiate sustained contractions, provided Ca2" was present during the exposure to caffeine. 5 It is concluded that caffeine can induce a sustained contraction after ryanodine treatment both in the guinea-pig gastric antrum and rabbit portal vein, by activating a Ca2+ influx pathway insensitive to organic Ca2+ channel blockers. No clear evidence was obtained for involvement of the Ca2' influx pathway activated through depletion of intracellular Ca2" stores. A hypothesis is proposed that the plasma membrane of these preparations is similar to the sarcoplasmic reticulum membrane in that Ca2+ permeability can be increased almost irreversibly by a combination of caffeine and ryanodine in the presence of the external Ca2+.

Caffeine and Ryanodine May Act on the Plasma Membrane of the Circular Muscle at the Flexure Region in the Guinea-Pig Colon.

“…On the contrary our results showed that caffeine induced phasic tran sient contraction under high concentration and it was abolished in Ca2+ free solution. This observation is consistent with the findings in guinea-pig gastric antrum (Chowdhury et al ., 1995) in which contractions induced by caffeine depend on Ca2+ influx. In the present experiment though in the guinea-pig gastric antrum contraction produced by 10 mM caffeine was resistant to verapamil (Chowdhury et al, 1995).…”

“…This observation is consistent with the findings in guinea-pig gastric antrum (Chowdhury et al ., 1995) in which contractions induced by caffeine depend on Ca2+ influx. In the present experiment though in the guinea-pig gastric antrum contraction produced by 10 mM caffeine was resistant to verapamil (Chowdhury et al, 1995). Thus it is likely that caffeine (10 mM) inducingcontraction in the flexure region is mainly due to the influx of Ca2+, because such contraction was abolished by removal of external Ca2+ and by Ca2+ channels blocker.…”

“…Those data are consistent with the results in the circular muscle of the guinea-pig gastric antrum and rabbit portal vein (Chowdhury et al, 1995) in which a continuous Ca2+ influx is necessary for the sustained contraction. Moreover, in our this result differed from the guinea-pig gastric antrum where the sustained contraction was insensitive to verapamil (Chowdhury et al, 1995).…”

“…We showed in the previous study that caffeine and ryanodine acted on the Ca2+ influx pathway of the plasma membrane rather than on the Ca2+ stores of the sarcoplasmic reticulum in the circular muscle of the guinea-pig gastric antrum (Chowdhury et al, 1995). Thus it seems useful to examine the effects of caffeine and ryanodine on the spontaneous rhythmic activity of the circular muscle at the flexure region in the guinea-pig colon.…”

“…For example in vascular smooth muscles (Itoh et al, 1981, Sato et al, 1988, caffeine produces a contraction in Ca2+ free solution, but it does not in the myometrium (Savineau and Mironneau, 1990) and in the guinea-pig gastric antrum (Chowdhury et al . , 1995).…”