Caffeine and carbachol act on common Ca2+ stores to release Ca2+ in guinea-pig ileal smooth muscle

Komori, Seiichi; Itagaki, Mitsue; Unno, Toshihiro; Ohashi, Hidenori

doi:10.1016/0014-2999(95)00072-s

Cited by 22 publications

(22 citation statements)

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“…We confirmed this blocking activity in preparations used for the present study, where YM-254890 abolished carbachol-evoked contractions mediated by intracellular Ca 2+ release that is known to involve G q/11 -type Gproteins [3,12,13]. In addition, YM-254890 had little effect on Ca 2+ sensitivity of contractile elements (Fig.…”

Section: Discussionsupporting

confidence: 83%

“…Two minutes later, carbachol was applied in the relaxing solution for 1-2 min to cause release of stored Ca 2+ , producing a brief tension development. The effect of carbachol is known to be mediated via activation of the M 3 receptor/G q/11 signaling pathway through the formation of the second messenger inositol 1,4,5-trisphosphate (IP 3 ) [3,12,13]. In order to determine the amount of remaining stored Ca 2+ , caffeine (20 mM), a potent Ca 2+ -releaser, was applied following carbachol stimulation.…”

Section: Methodsmentioning

confidence: 99%

“…It is well known that carbachol evokes intracellular Ca 2+ release via activating the M 3 receptor/G q/11 -type G-protein signaling system [3,12,13]. Therefore, tension responses upon Ca [12]. Subsequent application of 20 mM caffeine evoked a relatively small contraction, compared with the preceding carbachol-evoked contraction.…”

Section: +mentioning

confidence: 98%

“…We initially examined the ability of YM-254890 to block G q/11 -type G-proteins in -toxin-permeabilized skinned muscle strips used for the present study. It is well known that carbachol evokes intracellular Ca 2+ release via activating the M 3 receptor/G q/11 -type G-protein signaling system [3,12,13]. Therefore, tension responses upon Ca [12].…”

Section: +mentioning

confidence: 99%

“…Subsequent application of 20 mM caffeine evoked a relatively small contraction, compared with the preceding carbachol-evoked contraction. The caffeine contraction has been considered to be due to release of Ca 2+ remaining in the stores [12]. When the preparations were exposed to YM-254890 (1 M) during the 10-min Ca 2+ loading, carbachol was without effect, but subsequent caffeine evoked a prominent contraction (Fig.…”

Section: +mentioning

confidence: 99%

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Muscarinic Receptor Subtypes Mediating Ca2+ Sensitization of Intestinal Smooth Muscle Contraction: Studies with Receptor Knockout Mice

Suguro

Matsuyama

Tanahashi

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. In the present study, we have characterized muscarinic receptor subtypes that mediate carbachol-induced Ca 2+ sensitization of contraction in intestinal smooth muscle, using mutant mice lacking M 2 or M 3 muscarinic receptors or both receptor subtypes. In -toxinpermeabilized muscle strips from wild-type (WT) mice, isometric tension responses to Ca 2+ applied cumulatively (pCa 7.0-5.0) were increased when the muscarinic agonist carbachol (100 M) was added to the medium, as judged from shifts of pCa-tension curves in both 50% effective concentration (EC 50 ) and maximum response (E max ) of pCa-tension curve. In preparations from M 2 -knockout (KO) mice, pCa-tension curves were also shifted by carbachol (100 M), and the extents of the EC 50 and E max changes resembled those observed in preparations from WT mice. In preparations from M 3 -KO or M 2 /M 3 -double KO mice, however, no significant changes in pCa-tension curves were obtained after carbachol application. ] c to increase the MLCK/ MLCP activity ratio, resulting in enhanced contractions compared to those without receptor activation [21].In intestinal smooth muscles, acetylcholine and its derivatives such as carbachol, activate muscarinic receptors, inducing Ca 2+ sensitization as well as cytosolic Ca 2+ mobilization and contraction [6,29]. Among the five muscarinic receptor subtypes (M 1 -M 5 ), the M 2 and M 3 are predominantly expressed in intestinal smooth muscles [2]. By using muscarinic receptor antagonists with limited subtype selectivity, Murthy et al. [14] suggested that acetylcholineinduced Rho kinase activation and PKC activation in rabbit intestinal smooth muscles is mediated by the M 3 subtype, leading to Ca 2+ sensitization. However, such pharmacological studies often remain inconclusive because of the poor subtype selectivity of available muscarinic antagonists. For example, pharmacological studies suggested that carbacholevoked contractions are exclusively mediated by M 3 receptors, whereas recent studies using muscarinic receptor knockout mice implicated both M 3 and M 2 receptors in this response [30,31].Therefore, in the present study, using M 2 -knockout (KO) or M 3 -KO or M 2 /M 3 -double KO mice and wild type (WT) mice, we examined the activity of carbachol in inducing Ca 2+ sensitization in -toxin-permeabilized smooth muscles of the small intestine. In general, M 2 and M 3 muscarinic receptors are coupled preferentially with G i/o -and G q/11 -type G-proteins, respectively. We also examined whether the carbacholinduced Ca 2+ sensitization was affected by YM-254890, a selective inhibitor of G q/11 -type G-protein activity [23,26].

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Section: Discussionsupporting

confidence: 83%

Section: Methodsmentioning

confidence: 99%