ABSTRACT
Ginger [Zingiber officinale] is universally known food plant reputed for its medicinal use in gastrointestinal disorders as a prokinetic and laxative. We recently showed that 70% aqueous-methanolic extract of ginger [Zo.Cr] exhibits prokinetic activity in rats via activation of post-synaptic muscarinic M[3] receptor in rat stomach fundus. In view of the physiological significance of pre-synaptic muscarinic M[1] and M[2] autoreceptors, this study was undertaken to further look into the possible mode of action of the prokinetic effect of ginger through inhibition of pre-synaptic muscarinic receptors. Isolated tissue bath experiments were performed with Sprague-Dawley rat stomach fundus strip preparations immersed in Kreb's solution at 37 degree C. Carbachol [CCh] maximum responses [1 microM] were obtained in rat stomach fundus. Zo.Cr, given in multiple increasing bolus concentrations [0.01-0.1 mg/ml] 10 min prior to administration of CCh, potentiated the CCh peak responses showing that it is possibly inhibiting the pre-synaptic muscarinic receptors. Like wise, increasing bolus concentrations of pirenzepine [0.03-0.3 micro M] and himbacine [0.01-0.03 micro M], standard muscarinic M[1] and M[2] antagonists respectively, also potentiated the CCh responses. These results show that ginger, in addition to having a direct cholinergic effect on the post-synaptic M[3] receptors, also has a possible inhibitory effect on pre-synaptic muscarinic autoreceptors, similar to standard muscarinic antagonists, thus reiterating the gastric stimulant effect of this age-old plant
Subject(s)
Male , Female , Animals, Laboratory , Cholinergic Agents , Receptors, Muscarinic/drug effects , Autoreceptors , Stomach/drug effects , Gastric Fundus/drug effects , Rats, Sprague-DawleyABSTRACT
The non-selective beta-adrenoceptor antagonist, propranolol, has been reported to protect against gastric injury in mice, an effect only partly due to prostaglandin release. This study was designed to confirm the gastric cytoprotective effect of propranolol in another species of animal, the rat, and investigate further its mechanism of action. Our results show that propranolol prevents both ethanol-induced gastric lesions as well as ethanol-induced contraction of the circular muscle of rat fundic strip. The local anaesthetic, lignocaine also inhibited the effect of ethanol on circular muscle. However, timolol, another non-selective beta-adrenoceptor antagonist, failed to produce such an action. The effect of propranolol was abolished by the cyclooxygenase inhibitor, indomethacin and a high dose of the guanylate cyclase inhibitor, methylene blue. The results suggest that in addition to prostaglandins, endogenous nitric oxide and the membrane stabilising action of propranolol may also be involved in its gastroprotective action.
Subject(s)
Animals , Drug Interactions , Ethanol/antagonists & inhibitors , Gastric Fundus/drug effects , Gastrointestinal Hemorrhage/chemically induced , Indomethacin/pharmacology , Lidocaine/pharmacology , Male , Methylene Blue/pharmacology , Muscle Contraction/drug effects , Propranolol/therapeutic use , Rats , Rats, Inbred Strains , Stomach Diseases/chemically inducedABSTRACT
MK-212 (1 x 10(-7)M -- 1 x 10(-5)M) produced dose-dependent contractions of guinea pig ileum, taenia coil and rat fundus strip. The responses to MK-212 in all three preparations were blocked competitively by cyproheptadine (1 x 10(-8)M) a 5-HT receptor antagonist. Mepyramine (1 x 10(-8)M)-H1 receptor antagonist also inhibited competitively the responses of guinea pig ileum and taenia coli to MK-212. However, it failed to block significantly the responses of rat fundus strip to MK-212. Metiamide (1 x 10(-6)M), propranolol (1 x 10(-6)M) or atropine (1 x 10(-6)M) did not produce any significant effects on MK-212 induced contractile responses of guinea pig ileum, taenia coli and rat fundus strip. Our findings suggest that MK-212 produces both 5-HT as well as histamine like effects on the guinea-pig ileum, taenia coli and rat fundus strip.