Erowid References Database
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Drew GM.
“Pharmacological Characterization of the Presynaptic a-Adrenoreceptors Regulating Cholinergic Activity in the Guinea-Pig Ileum”.
Brit.J.Pharmacol.. 1978;64(2):293-300.
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Abstract
The effect of drugs on presynaptic a-adrenoceptors regulating cholinergic activity in the guinea-pig ileum was studied. Guinea-pigs (Duncan Hartley-Porcellus, 300-400 g) were killed by cervical dislocation and a piece of ileum suspended in an organ bath. Intramural nerves were stimulated electrically and contractions recorded isometrically. Propranolol (0.3 mcg/ml) was added to block beta-adrenoceptors. The concentration of a agonist required to reduce the twitch response to electrical stimulation by 50% was found, and if piperoxan (May and Baker, 0.3-1 mcg/ml) reversed the twitch inhibition it was assumed that the agonist worked via a-adrenoceptors. The effect of clonidine (Boehringer Ingelheim) on ACh (BDH) induced contractions was measured. Then the effect of clonidine on the twitch response in the pressure and absence of antagonist was determined, and repeated. In some experiments morphine (MacFarlan Smith) was used in place of clonidine. Atropine (BDH, 1 mcg/ml) abolished the electrically stimulated twitch response, whereas hexamethonium (10-30 mcg/ml) only reduced it by 10%. Thus, the nerves involved were cholinergic and mainly post ganglionic. Clonidine (0.1-30 ng/ml) caused dose dependent reductions in the twitch response, to a maximum of 80 95%. Hexamethonium did not alter this. Oxymetazoline (Merck) and xylazine (Bayer AG) were 5 times less potent and phenylephrine (Koch-Light) and methoxamine (Borroughs Wellcome) were 10,000 times less potent than clonidine. Piperoxan (0.3-1 g/ml) reversed the inhibitory effects of clonidine, oxymetazoline and xylazine, but not those of phenylephrine or methoxamine. LSD (Sandoz, 0.01-3 mcg/ml) increased basal tone and reduced the size of the twitch response up to 60%. Mepyramine (May and Baker, 10-100 mcg/ml) prevented the LSD-induced increase in tone without affecting its twitch inhibition. LSD inhibition of twitch was only partially blocked by piperoxane or phentolamine. Phentolamine (CIBA), yohimbine (Sigma), piperoxan and tolazoline (CIBA) were potent competitive antagonists of clonidine,whereas thymoxamine (Warner) had an antagonistic effect on morphine as well as clonidine twitch inhibition. Labetolol (AH5158, Allen and Hanbury 0.3 mcg/ml) depressed the twitch response but did not inhibit the residual effect of clonidine. The presynaptic a-adrenoceptors in the guinea-pig ileum are of the a2-type and differ from those located postsynaptically.
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