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)
Haynes
J M
JM
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Pennefather
J N
JN
D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism*; D010627:Phenethylamines / Q000378:metabolism / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000378:metabolism / Q000494:pharmacology; D011869:Radioligand Assay; D011983:Receptors, Purinergic / Q000187:drug effects / Q000378:metabolism*; D013805:Theobromine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014970:Xanthines / Q000378:metabolism / Q000494:pharmacology
D010627:Phenethylamines; D011983:Receptors, Purinergic; D014970:Xanthines; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D010656:Phenylephrine; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); C057837:3,7-dimethyl-1-propargylxanthine; D000242:Cyclic AMP; C046379:1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine; D000241:Adenosine; D013805:Theobromine