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 series of agonists and antagonists. 2. The tissue was precontracted with carbachol (1 microM), and the purines induced reversible relaxations with a potency order of 5'-N-ethylcarboxamidoadenosine (NECA) greater than N6-cyclopentyladenosine (CPA) = adenosine 5'-(alpha, beta-methylene) triphosphonate (AMPCPP) greater than adenosine = adenylyl 5'-(beta, gamma-methylene) disphosphonate (AMPPCP) = ATP. The P1-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (3 microM) shifted to the right the log concentration-response curves of all these agonists except for AMPCPP, indicating that they all act via P1-purinoceptors. The order of potency of the adenosine analogues and the relatively high concentrations of the antagonist required indicated that these receptors are of the A2 subtype. The P2-selective antagonist suramin (300 microM) inhibited responses to AMPCPP, but not to the other agonists. 3. The dephosphorylation of the nucleotides was studied by high performance liquid chromatography following incubation with the longitudinal muscle preparation for up to 30 min. ATP was rapidly degraded, largely to adenosine, and AMPPCP and AMPCPP were also degraded, although more slowly, to adenosine and adenosine 5'-(alpha, beta-methylene) diphosphonate (AMPCP) respectively. AMPCP, like AMPCPP, caused relaxations by acting on P2-purinoceptors, as it was also inhibited by suramin (300 microM). Incubation of the tissue with adenosine deaminase abolished responses to adenosine, reduced those to ATP and AMPPCP, but had no effect on those to AMPCPP.(ABSTRACT TRUNCATED AT 250 WORDS)
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