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Adenosine‐ and α,β‐methylene ATP‐induced differential inhibition of cholinergic and non‐cholinergic neurogenic responses in rat urinary bladder
Author(s) -
Parija S.C.,
Raviprakash V.,
Mishra S.K.
Publication year - 1991
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.1476-5381.1991.tb12185.x
Subject(s) - adenosine , cholinergic , acetylcholine , endocrinology , medicine , chemistry , stimulation , purinergic receptor , physostigmine , adenosine triphosphate , atropine , biology
1 The effects of adenosine and α,β‐methylene adenosine triphosphate (α,β‐Me ATP) on single pulse‐induced neurogenic responses and contractions caused by exogenously applied acetylcholine (ACh) and adenosine triphosphate (ATP) were examined in rat urinary bladder. 2 Application of single pulse stimulation (1 ms; 80 V) evoked a biphasic contractile response (abolished by tetrodotoxin, 0.5 × 10 −7 m ) consisting of a fast (time to peak: 1.02 ± 0.07 s) and a slow component (time to peak: 4.92 ± 1.6 s). The selective inhibition of the slow component by atropine (3 × 10 −6 m ) suggests the participation of both cholinergic and non‐cholinergic neurotransmitters. 3 α,β‐Me ATP (5 × 10 −6 m ) abolished ATP (10 −4 m )‐induced contractions without altering those to ACh (10 −6 m ). Further, the selective inhibition of the fast component of the neurogenic response by α,β‐Me ATP is suggestive of the contribution of endogenous ATP to the non‐cholinergic component. 4 Adenosine (10 −8 m to 10 −4 m ) caused dose‐related differential inhibition of the fast (IC 50 , 1.04 ± 0.25 × 10 −5 m ) and slow (IC 50 , 2.18 ± 0.69 × 10 −6 m ) components, thereby further supporting two modes of neurotransmission in bladder. 5 Theophylline (10 −4 m ) antagonized the inhibitory effects of adenosine on the non‐cholinergic component, thereby implicating the participation of P 1 ‐purinoceptors in neuromodulation. In contrast, theophylline at this concentration enhanced the adenosine‐induced inhibition of the cholinergic component. 6 The magnitude of ATP (10 −4 m )‐ and ACh (10 −8 m )‐induced contractions were almost identical to those of the fast and slow components of the neurogenic response, respectively. Comparable reduction of ATP (30.2 ± 3.4%) and ACh (100%) contractions to those of fast (44.2 ± 6.5%) and slow (88.2 ± 5.5%) components suggests the involvement of a postjunctional mechanism in adenosine‐induced differential inhibition of neurogenic responses. 7 The lack of effect of erythro‐6‐amino‐9‐(2‐hydroxy‐3‐nonyl) adenosine hydrochloride (10 −6 m ) and dipyridamole (10 −6 m ) suggests that endogenous adenosine plays little part in modulation of single pulse‐induced neurogenic response. 8 The results of the present study suggest that fast and slow components of neurogenic response are mediated through ATP and ACh, respectively, possibly co‐released from the same neurone in the rat bladder.