Dual action of ranitidine at cholinergic sites in the rat isolated anococcygeus muscle

1. The effects of ranitidine on contractile responses of the rat isolated anococcygeus muscle to acetylcholine (ACh) and carbachol (CCh) were investigated. 2. Four consecutive cumulative concentration-response curves (CRCs) for ACh or CCh were constructed in the absence or presence of ranitidine. The mean EC50 values were determined from the individual CRCs and used for the calculation of the corresponding EC50 ratios. 3. Ranitidine (0.01, 0.05 and 0.5 mM) produced a progressively leftward shift of the ACh curves; the corresponding EC50 ratios obtained were 3.2 +/- 0.4, 5.7 +/- 0.5 and 9.4 +/- 1.4. Neostigmine 0.5 microM alone or in combination with ranitidine 0.1 mM produced very marked leftward shifts of the ACh curves (EC50 ratios 68.2 +/- 14.3 and 56.3 +/- 9.6 respectively). In contrast, ranitidine (0.05, 0.5 and 2 mM) produced a rightward and parallel shift of the CCh curves (EC50 ratios 1.0 +/- 0.1, 3.4 +/- 0.32 and 12.5 +/- 1.7 respectively). 4. Ranitidine can therefore mediate a dual action at cholinergic sites in the rat isolated anococcygeus muscle, actions which can be attributed to its inherent anticholinesterase and antimuscarinic activity. The relatively marked anticholinesterase action of ranitidine was rather surprising in view of the limited cholinergic innervation present in the rat anococcygeus muscle.