Neurally evoked potentiation of tonic contractions in the guinea-pig vas deferens involves adenosine receptors.
1. In the pelvic plexus-vas deferens preparation of the guinea-pig, conditioning stimulation of the pelvic nerves depressed the phasic component of biphasic contractions evoked by test stimulation of the hypogastric nerves, but potentiated the tonic component. 2. Similarly, in the deganglionated vas deferens preparation, conditioning stimulation applied directly to postganglionic nerves issuing from the pelvic nerve side of the pelvic plexus depressed the phasic component of biphasic contractions evoked by test stimulation of the nerves issuing from the plexus on the side of the hypogastric nerve, but potentiated the tonic component. 3. In the deganglionated preparation in the presence of alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-mATP) by which the phasic component was removed, test contractions were markedly reduced by phentolamine and prazosin, and potentiated in a manner dependent on the magnitude of conditioning stimulation. 4. In the deganglionated preparations that were persistently exposed to alpha,beta-mATP (5-10 microM), attempts were made to identify the substance(s) mediating the potentiation of the prazosin-sensitive contractions and their sites of action. 5. Noradrenaline and neuropeptide Y depressed the test contractions. 6. ATP, adenosine 5'-diphosphate, adenosine 5'-monophosphate and adenosine potentiated the contractions. Inosine and adenine were without effect. The effect of ATP was antagonized by 8-phenyltheophylline. N6-Cyclohexyladenosine (CHA) potentiated the contractions in a dose-dependent and 8-phenyltheophylline-sensitive manner. 7. The conditioning stimulation-induced potentiation of test contractions was antagonized by 8-phenyltheophylline, but was further increased by dipyridamole. 8. Methoxamine-evoked contractions were potentiated by conditioning stimulation of the nerves in a manner antagonized by 8-phenyltheophylline, and also by CHA. 9. Adenosine and CHA inhibited in an 8-phenyltheophylline-sensitive manner field stimulation-induced release of 3H-activity from deganglionated vas deferens preloaded with [3H]noradrenaline. 10. In the deganglionated preparation that was not exposed to alpha, beta-mATP, ATP-evoked contractions were potentiated by conditioning stimulation and by CHA. 11. It is indicated that conditioning stimulation and adenosine exert opposite actions on phasic and on tonic contractions in spite of the results showing that each of them postjunctionally potentiates the responses to both ATP and noradrenaline. 12. These results suggest that conditioning stimulation releases adenosine and that adenosine potentiates tonic contractions by increasing the responsiveness of the muscle to noradrenaline through the postjunctional adenosine receptors.
Tsunoo
A
A
Meiji Institute of Health Science, Odawara, Japan.
Kurokawa
M
M
Takahashi
K
K
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003714:Denervation; D004176:Dipyridamole / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D014649:Vas Deferens / Q000187:drug effects / Q000294:innervation* / Q000502:physiology*
D011983:Receptors, Purinergic; C027513:N(6)-cyclohexyladenosine; D004176:Dipyridamole; D000255:Adenosine Triphosphate; D000243:Adenosine Deaminase; D000241:Adenosine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate