EFFECTS OF PURINES ON THE LONGITUDINAL MUSCLE OF THE RAT COLON

Citation
Sj. Bailey et Smo. Hourani, EFFECTS OF PURINES ON THE LONGITUDINAL MUSCLE OF THE RAT COLON, British Journal of Pharmacology, 105(4), 1992, pp. 885-892
Citations number
48
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
885 - 892
Database
ISI
SICI code
0007-1188(1992)105:4<885:EOPOTL>2.0.ZU;2-V
Abstract
1 Adenosine and adenosine 5'-triphosphate (ATP) have been reported to cause relaxation of the rat colon longitudinal muscle preparation; the purinoceptors mediating this effect were investigated by use of a ser ies of agonists and antagonists. 2 The tissue was precontracted with c arbachol (1-mu-M), and the purines induced reversible relaxations with a potency order of 5'-N-ethylcarboxamidoadenosine (NECA) >N6-cyclopen tyladenosine (CPA) = adenosine 5'-(alpha,beta-methylene) triphosphonat e (AMPCPP) > adenosine = adenylyl 5'-(beta,gamma-methylene) disphospho nate (AMPPCP) = ATP. The P1-selective antagonist 1,3-dipropyl-8-cyclop entylxanthine (DPCPX) (3-mu-M) shifted to the right the log concentrat ion-response curves of all these agonists except for AMPCPP, indicatin g that they all act via P1-purinoceptors. The order of potency of the adenosine analogues and the relatively high concentrations of the anta gonist required indicated that these receptors are of the A2 subtype. The P2-selective antagonist suramin (300-mu-M) inhibited responses to AMPCPP, but not to the other agonists. 3 The dephosphorylation of the nucleotides was studied by high performance liquid chromatography foll owing incubation with the longitudinal muscle preparation for up to 30 min. ATP was rapidly degraded, largely to adenosine, and AMPPCP and A MPCPP were also degraded, although more slowly, to adenosine and adeno sine 5'-(alpha,beta-methylene) diphosphonate (AMPCP) respectively. AMP CP, like AMPCPP, caused relaxations by acting on P2-purinoceptors, as it was also inhibited by suramin (300-mu-M). Incubation of the tissue with adenosine deaminase abolished responses to adenosine, reduced tho se to ATP and AMPPCP, but had no effect on those to AMPCPP. ATP and AM PPCP therefore appear to be acting on the A2 receptors in this tissue largely via their degradation product adenosine. 4 The longitudinal mu scle of the rat colon therefore contains both P1- and P2-purinoceptors , which both mediate relaxation. The P1-purinoceptors are of the A2 su btype and the P2-purinoceptors are probably of the P2y subtype, althou gh the rapid degradation of the nucleotides means that it is difficult to classify them with certainty.