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Pharmacological characterization of adenosine A 1 and A 2 receptors in the bladder: evidence for a modulatory adenosine tone regulating non‐adrenergic non‐cholinergic neurotransmission
Author(s) -
Acevedo Carmen Gloria,
Contreras Enrique,
Escalona Juan,
Lewin Jorge,
HuidobroToro J. Pablo
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14473.x
Subject(s) - adenosine , endocrinology , medicine , adenosine receptor , guanethidine , purinergic receptor , stimulation , biology , muscle contraction , carbachol , nucleoside , neurotransmission , chemistry , receptor , agonist , biochemistry
1 The nerve‐evoked contractions elicited by transmural electrical stimulation of mouse urinary bladders superfused in modified Krebs Ringer buffer containing 1 μ m atropine plus 3.4 μ m guanethidine were inhibited by adenosine (ADO) and related nucleoside analogues with the following rank order of potency: R ‐phenylisopropyladenosine ( R ‐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) > R ‐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 μ m NECA not only reduced the motor responses elicited by ATP, but also 5‐hydroxytryptamine, acetylcholine and prostaglandin F 2α. The action of NECA was antagonized following tissue preincubation with 8‐PT. The inhibitory action of NECA was not mimicked by 10 μ m CHA. 4 The maximal bladder ATP contractile response was significantly increased by tissue preincubation with 5–30 μ 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‐A 1 and A 2 receptors in the mouse urinary bladder. The A 1 receptor subpopulation is probably of presynaptic origin whereas the smooth muscle membranes contain a population of the A 2 receptor subtype.