PHARMACOLOGICAL CHARACTERIZATION OF ADENOSINE-A1 AND A2 RECEPTORS IN THE BLADDER - EVIDENCE FOR A MODULATORY ADENOSINE TONE REGULATING NONADRENERGIC NONCHOLINERGIC NEUROTRANSMISSION
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Date
1992
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Abstract
1 The nerve-evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1-mu-M atropine plus 3.4-mu-M guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: RB-phenylisopropyladenosine (RB-PIA) > cyclohexyladenosine (CHA) > 5'N-ethylcarboxamido adenosine (NECA) > ADO > 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 > 2-chloroadenosine (CADO) > RB-PIA > ADO > CHA > S-PIA.
3 The ADO-induced ATP antagonism was of a non-competitive nature and was not specific. Tissue incubation with 10-mu-m 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-mu-m CHA.
4 The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5-30-mu-m 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-A1 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.
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 > 2-chloroadenosine (CADO) > RB-PIA > ADO > CHA > S-PIA.
3 The ADO-induced ATP antagonism was of a non-competitive nature and was not specific. Tissue incubation with 10-mu-m 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-mu-m CHA.
4 The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5-30-mu-m 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-A1 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.
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NONNORADRENERGIC NONCHOLINERGIC NEUROTRANSMISSION, PURINERGIC TRANSMISSION, ADENOSINE RECEPTORS, ADENOSINE A1, A2 MECHANISMS, ADENOSINE MODULATION, URINARY BLADDER