A1- and A2-purinoceptors in the guinea-pig uterus

1. Radioligand binding and functional studies were undertaken to investigate the P1-purinoceptors present in the separated myometrial layers and the endometrium of the guinea-pig uterus. 2. In preparations of endometrium-denuded circular myometrium, the A2-selective agonists (2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamido-adeno sin e (CGS 21680, 100 mumol/L) and N-ethylcarboxamido adenosine (NECA, 1-10 mumol/L) inhibited contractile responses to phenylephrine. In preparations of endometrium-intact circular myometrium, NECA (10 mumol/L) enhanced responses to phenylephrine. NECA did not modulate the spontaneous contractions of longitudinal myometrium. 3. Homogenate binding studies with circular myometrium, longitudinal myometrium and endometrium revealed saturable high affinity [3H]-NECA binding sites. The mean maximal densities of binding sites (Bmax) were 2.08, 14.7 and 15.5 fmol/mg protein, and pKD (neg. log dissociation constant) values were 9.82, 9.19 and 7.44, respectively. 4. (R-) and (S-)-N6-(2-phenylisopropyl)adenosine (R- and S-PIA) both competed for two [3H]-NECA binding sites in preparations of circular myometrium. CGS 21680 competed for two [3H]-NECA binding sites in preparations of endometrium and longitudinal myometrium. All other agonist competition was for one site only. The rank orders of potency of high affinity binding were S-PIA > or =R-PIA > or = CGS 21680 (circular myometrium), R-PIA > CGS 21680 > or = S-PIA (longitudinal myometrium) and CGS 21680 > > S-PIA > or = R-PIA (endometrium). 5. In preparations of circular myometrium, longitudinal myometrium and endometrium the selective A1-purinoceptor antagonist, 1,3-dipropyl-8-(2-amino-4-chloro)-phenylxanthine (PACPX), competed for two [3H]-NECA binding sites, the non-selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX), competed for one site only.(ABSTRACT TRUNCATED AT 250 WORDS)