Contractile responses of smooth muscle strips from rat and guinea-pig urinary bladder to transmural stimulation: effects of atropine and alpha,beta-methylene ATP.
1. Strength-duration curves for threshold mechanical responses to single transmural stimuli were identical for rat and guinea-pig detrusor. In both species atropine had no effect on the curves, but the curves were shifted to the right by nerve blockade with tetrodotoxin (TTX), and by blockade of P2-purinoceptors with alpha,beta-methylene ATP (alpha,beta-MeATP). 2. With short duration pulses of 50 V and less, the responses were nerve-mediated. Increase in either the strength or duration of the stimulus caused direct muscle stimulation, resistant to blockade with atropine, TTX and alpha-beta-MeATP. 3. The shape of the contractile response to a single nerve stimulus varied from tissue to tissue. The responses could be mono-, bi-, or multiphasic. Bi- or multiphasic responses were normally seen in tissues which were spontaneously active. The multiphasic nature of the response was enhanced by factors which increased the excitability of the cells and was reduced by factors which decreased the excitability. 4. The frequency-response curves in the rat are similar to those previously obtained in the guinea-pig. Atropine suppresses the high frequency response by 25%, with little effect at low frequencies, whereas desensitization of P2-purinoceptors with alpha,beta-MeATP suppresses the responses maximally at low frequencies but still by 75% at high frequencies. A combination of both drugs eliminates the nerve-mediated responses. 5. It is concluded that the response to a single nerve stimulus is mediated by a non-cholinergic transmitter, through activation of P2-purinoceptors. The possibility that simultaneous release of acetylcholine can modify the excitability of cells and thus the configuration of the response to a single stimulus is discussed.
Brading
A F
AF
University Department of Pharmacology, Oxford.
Williams
J H
JH
D000109:Acetylcholine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D013045:Species Specificity; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
D011976:Receptors, Muscarinic; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D001285:Atropine; D000255:Adenosine Triphosphate; D000109:Acetylcholine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate