Ranitidine inhibits adrenergic but not nonadrenergic noncholinergic transmission in the rat isolated anococcygeus muscle.
The effects of ranitidine on adrenergic and nonadrenergic noncholinergic transmission in the rat isolated anococcygeus muscle and on the contractile responses of the muscle to noradrenaline, potassium chloride, 5-hydroxytryptamine and carbachol were investigated. Ranitidine (2-8 mM) produced a concentration-dependent and readily reversible inhibition of motor (excitatory) responses of the anococcygeus muscle evoked via field stimulation (20-30 V, 10 Hz x 10 sec, 1 msec pulse width, every 2 min), whereas the contractile response of the anococcygeus muscle to exogenous noradrenaline (3 microM) was potentiated by 57 +/- 3.7%; the contractile response to potassium chloride (50 mM) was only slightly decreased, whereas the responses to carbachol (3 microM) or 5-hydroxytryptamine (30 microM) were completely inhibited by ranitidine (8 mM). When the tone of the muscle was raised by noradrenaline (3 microM) after complete inhibition of the motor responses by ranitidine (8 mM), field stimulation produced relaxant (inhibitory) responses which were inhibited by tetrodotoxin (2 microM) or NG-nitro-L-arginine methylester (50 microM). Similar results were obtained with guanethidine (0.5-3 microM) on adrenergic and non-adrenergic noncholinergic transmission. The results clearly show that ranitidine can selectively inhibit adrenergic transmission in the anococcygeus muscle with consequent unmasking of nonadrenergic noncholinergic transmission; ranitidine can also produce a super-sensitivity-type response of the muscle to exogenous noradrenaline but not to potassium chloride, carbachol or 5-hydroxytryptamine. Thus, the inhibition of adrenergic transmission by ranitidine in the rat isolated anococcygeus muscle closely resembles the action of guanethidine on adrenergic transmission.
Department of Pharmacology, Faculty of Medicine, National University of Singapore.
M C
MC
Gwee
L S
LS
Cheah
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology; D003864:Depression, Chemical; D003891:Desipramine / Q000494:pharmacology; D006145:Guanethidine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000294:innervation*; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology
D012701:Serotonin; D013779:Tetrodotoxin; D011189:Potassium Chloride; D011899:Ranitidine; D002217:Carbachol; D001120:Arginine; D003891:Desipramine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D006145:Guanethidine