Action mechanisms of the contracting drugs, K, acetylcholine, histamine and Ba and of the antispasmodics, isoproterenol and papaverine in the isolated guinea pig ileum, particularly in relation to Ca

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Abstract
The contractions induced by K, acetylcholine (ACh), histamine and Ba consisted of the phasic contraction (PC) and subsequent tonic contraction (TC). PCs by K, ACh and histamine are initiated by the release and the passive influx of Ca; that by Ba is only initiated by the release of Ca. TCs by K, ACh and histamine are maintained by the active influx of Ca; that by Ba is maintained by the active influx and the release of Ca. Storage sites of Ca in the cell membrane of this preparation can be divided into the 1st, the 2nd and the 3rd, which contain the loosely, the less loosely, and the tightly-bound Ca, respectively. K releases Ca to elicit contraction from the 1st divisions; ACh or histamine does so from the 1st and 2nd divisions; and Ba does so from all 3 divisions. Based on the influence of high K-depolarizing bath solution on the relaxations by isoproterenol (Iso) and papaverine (Pap) and the effects of Iso and Pap on the shapes of contractions by K, ACh, Ba and exogenous Ca, the following assumptions were made: antispasmodic action of Iso is produced by inhibition of cell membrane (inhibition of release and influx of Ca); that by Pap is due to this inhibition followed by inhibition of the muscle contractile system with the increase of concentrations. The effects of Iso and Pap on the concentration-action curves of the contractions by K, ACh, Ba and exogenous Ca suggest that the parallel shift to the right of the curves of K, ACh and Ba is due to the functional antagonism between the antispasmodics and the mobilization of Ca produced by the contracting agents.