Pharmacological characterization of adenosine A1 and A2 receptors in the bladder: evidence for a modulatory adenosine tone regulating non-adrenergic non-cholinergic neurotransmission.
1. The nerve-evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1 microM atropine plus 3.4 microM guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: R-phenylisopropyladenosine (R-PIA) greater than cyclohexyladenosine (CHA) greater than 5'N-ethylcarboxamido adenosine (NECA) greater than ADO greater than S-phenylisopropyladenosine (S-PIA). Tissue preincubation with 8-phenyltheophylline (8-PT) displaced to the right, in a parallel fashion, the NECA concentration-response curve. 2. The contractions elicited by application of exogenous adenosine 5'-triphosphate (ATP) were also inhibited by ADO and related structural analogues. The rank order of potency to reduce the motor response to ATP was: NECA greater than 2-chloroadenosine (CADO) greater than R-PIA greater than ADO greater than CHA greater than S-PIA. 3. The ADO-induced ATP antagonism was of a non-competitive nature and was not specific. Tissue incubation with 10 microM NECA not only reduced the motor responses elicited by ATP, but also 5-hydroxytryptamine, acetylcholine and prostaglandin F2 alpha. The action of NECA was antagonized following tissue preincubation with 8-PT. The inhibitory action of NECA was not mimicked by 10 microM CHA. 4. The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5-30 microM 8-PT. 5. The 0.15 Hz evoked muscular twitch was significantly increased by 8-PT while dipyridamole consistently reduced the magnitude of the twitch response. These results are consonant with the hypothesis that an endogenous ADO tone modulates the bladder neurotransmission. 6. A working model is proposed suggesting the presence of ADO-Al and A2 receptors in the mouse urinary bladder. The A1 receptor subpopulation is probably of presynaptic origin whereas the smooth muscle membranes contain a population of the A2 receptor subtype.
Acevedo
C G
CG
Department of Pharmacology, Faculty of Biological Sciences and Natural Resources, University of Concepción, Santiago, Chile.
Contreras
E
E
Escalona
J
J
Lewin
J
J
Huidobro-Toro
J P
JP
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D004176:Dipyridamole / Q000494:pharmacology; D004558:Electric Stimulation; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D001743:Urinary Bladder / Q000187:drug effects / Q000294:innervation* / Q000502:physiology
D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D004176:Dipyridamole; D000255:Adenosine Triphosphate; D013806:Theophylline; C028322:8-phenyltheophylline; D000241:Adenosine