CHARACTERIZATION OF THE ADENOSINE RECEPTOR MEDIATING CONTRACTION IN RAT COLONIC MUSCULARIS MUCOSAE

1 The objective of this study was to characterize the adenosine recept or mediating contraction in rat isolated colonic muscularis mucosae (R CMM). 2 Sequential additions of the adenosine receptor agonist 5'-N-et hylcarboxamidoadenosine (NECA; 0.01-10 muM) elicited reproducible, con centration-related contractions in RCMM. The effects of NECA were mimi cked by the adenosine A1 receptor-selective agonists cyclopentyladenos ine (CPA), R-phenylisopropyladenosine (R-PIA) and N-[1S, trans)2-hydro xycyclopentyl] adenosine (GR79236) and by S-PIA (the stereoisomer of R -PIA). The adenosine A2 agonists N-[(2-methylphenyl)methyl] adenosine (metrifudil) and hyl)phenethylamine]-5'-N-ethylcarboxamidoadenosine (C GS21680) 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 greater-than-or-equal-to GR79236 = R-P IA greater-than-or-equal-to NECA>>S-PIA = metrifudil>CGS21680, which i s 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 behav ed as partial agonists in RCMM. 4 The adenosine A1 receptor-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) inhibited the co ntractions produced by all the adenosine agonists tested, with pK(B) v alues between 9.2 and 9.5. The non-selective adenosine antagonist 8-ph enyltheophylline (8-PT) antagonized the effects of NECA but also marke dly potentiated (by 93.0 +/- 10.2% at 3 muM) the maximum contractile r esponse to NECA in RCMM. Neither 8-PT (3 muM) nor DPCPX (0.1 muM) had any effect on the contractions produced by carbachol. 5 The contractil e responses to NECA in RCMM were not affected by atropine (1 muM), tet rodotoxin (0.3 muM) or the P2 antagonist, suramin (100 muM). 6 The pre sent study confirms that contractions to adenosine agonists in the RCM M are mediated via adenosine A1 receptors.