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Characterization of the adenosine receptor mediating contraction in rat colonic muscularis mucosae
Author(s) -
Reeves J.J.,
Coates J.,
Jarvis J.E.,
Sheehan M.J.,
Strong P.
Publication year - 1993
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.1476-5381.1993.tb13950.x
Subject(s) - adenosine , adenosine receptor , medicine , agonist , endocrinology , contraction (grammar) , adenosine a1 receptor , muscularis mucosae , adenosine receptor antagonist , muscle contraction , chemistry , biology , receptor
1 The objective of this study was to characterize the adenosine receptor mediating contraction in rat isolated colonic muscularis mucosae (RCMM). 2 Sequential additions of the adenosine receptor agonist 5′‐ N ‐ethylcarboxamidoadenosine (NECA; 0.01–10 μ m ) elicited reproducible, concentration‐related contractions in RCMM. The effects of NECA were mimicked by the adenosine A 1 receptor‐selective agonists cyclopentyladenosine (CPA), R ‐phenylisopropyladenosine ( R ‐PIA) and N‐[1 S , trans )2‐hydroxycyclopentyl] adenosine (GR79236) and by S ‐PIA (the stereoisomer of R ‐PIA). The adenosine A 2 agonists N‐[(2‐methylphenyl)methyl] adenosine (metrifudil) and 2‐[ p ‐(2‐carboxyethyl)phenethylamine]‐ 5′‐ N ‐ethylcarboxamidoadenosine (CGS21680) also produced contractions in RCMM but were 54 and 165 times less potent respectively than NECA. The rank order of agonist potency for contraction of RCMM was CPA ≥ GR79236 = R ‐PIA ≥ NECA >> S ‐PIA = metrifudil > CGS21680, which is identical to that reported for the inhibition of spontaneous rate in rat isolated right atria and inhibition of lipolysis in rat isolated adipocytes by these same agonists. 3 R ‐PIA, S ‐PIA and metrifudil behaved as partial agonists in RCMM. 4 The adenosine A 1 receptor‐selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) inhibited the contractions produced by all the adenosine agonists tested, with p K B values between 9.2 and 9.5. The non‐selective adenosine antagonist 8‐phenyltheophylline (8‐PT) antagonized the effects of NECA but also markedly potentiated (by 93.0 ± 10.2% at 3 μ m ) the maximum contractile response to NECA in RCMM. Neither 8‐PT (3 μ m ) nor DPCPX (0.1 μ m ) had any effect on the contractions produced by carbachol. 5 The contractile responses to NECA in RCMM were not affected by atropine (1 μ m ), tetrodotoxin (0.3 μ m ) or the P 2 antagonist, suramin (100 μ m ). 6 The present study confirms that contractions to adenosine agonists in the RCMM are mediated via adenosine A 1 receptors.