Characterization of the adenosine receptor mediating contraction in rat colonic muscularis mucosae

Abstract

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 gM) elicited reproducible, concentration-related contractions in RCMM. The effects of NECA were mimicked by the adenosine Al receptor-selective agonists cyclopentyladenosine (CPA), Rphenylisopropyladenosine (R-PIA) and N-[1S, trans)2-hydroxycyclopentyl] adenosine (GR79236) and by S-PIA (the stereoisomer of R-PIA). The adenosine A2 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. 5 The contractile responses to NECA in RCMM were not affected by atropine (1 JiM), tetrodotoxin (0.3 JAM) or the P2 antagonist, suramin (100IM). 6 The present study confirms that contractions to adenosine agonists in the RCMM are mediated via adenosine Al receptors.

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

“…However, immunohistochemical expression of P2X1 receptors in the smooth muscle of the muscularis mucosae, but not the muscularis externa, suggested that P2X1 rather than P2Y receptors were involved. The presence of P1 (A 1 ) receptors in rat colon muscularis mucosae, mediating contraction, was confirmed in a later study [566], although part of the response was claimed to be due to products of the cyclooxygenase pathway [567]. ATP inhibited swelling-activated Cl − currents in canine colonic smooth muscle, and it was suggested that this may be related to the regulation of myogenic activation in response to distension [181].…”

Further investigations into adenosine A1 receptor‐mediated contraction in rat colonic muscularis mucosae and its augmentation by certain alkylxanthine antagonists

“…Contractions were produced by the non-selective adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA); the adenosine Al-selective agonists, cyclopentyladenosine (CPA), R-phenylisopropyladenosine (R-PIA) and N[(lS,trans)-2-hydroxycyclopentyl]adenosine (GR79236) and by the A2-selective agonists, metrifudil and 2-[p- (2-carboxyethyl) phenylethyl amine)-5'-N-ethylcarboxamidoadenosine (CGS21680). The rank order of agonist potency (CPA > GR79236 = R-PIA > NECA>metrifudil>CGS21680; Reeves et al, 1993b) was identical to that obtained for the ' Author for correspondence. inhibition of spontaneous rate in rat isolated right atria and the inhibition of lipolysis in rat isolated adipocytes, two adenosine A1 receptor containing preparations (Gurden et al, 1993).…”

“…We also found that the non-selective adenosine A,/A2 receptor antagonist, 8-phenyltheophylline (8-PT;Collis et al, 1985), not only antagonized concentration-effect curves to NECA but also augmented its maximum response (Reeves et al, 1993b). The purpose of the present study therefore was to investigate further the characteristics of this augmentation by the use of a number of different adenosine receptor agonists and antagonists.…”

“…In addition, some experiments were performed in an attempt to determine the mechanism of this augmentation. Preliminary accounts of this work have been presented to the British Pharmacological Society (Reeves et al, 1993a;Jarvis et al, 1994).…”

“…We and others (Bailey et al, 1992;Reeves et al, 1993b) have previously reported that adenosine agonists produced contractions in the rat isolated colonic muscularis mucosae (RCMM). Contractions were produced by the non-selective adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA); the adenosine Al-selective agonists, cyclopentyladenosine (CPA), R-phenylisopropyladenosine (R-PIA) and N[(lS,trans)-2-hydroxycyclopentyl]adenosine (GR79236) and by the A2-selective agonists, metrifudil and 2-[p- (2-carboxyethyl) phenylethyl amine)-5'-N-ethylcarboxamidoadenosine (CGS21680).…”