Evidence for the presence of both P1 and P2 purinoceptors in the rat myometrium

1. Adenosine, adenosine triphosphate (ATP) and some stable analogues of adenosine inhibited field stimulation-induced contractions of the uterus from rats treated with oestradiol cypionate (20 mu g/kg, s.c.) 1 day previously, Adenosine was twice as potent as ATP; both were potentiated by dipyridamole (10 mu mol/L). 2. The order of agonist potency of adenosine and its analogues was: 5'-N-ethylcarboxamidoadenosine (NECA) > N-6-cyclohexyladenosine greater than or equal to R-phenylisopropyladenosine = s-phenylisopropyladenosine = 2-chloroadenosine greater than or equal to adenosine 2 ATP much greater than 2-p-(2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine. This order suggests the presence of P-1 purinoceptors of the A(2B) subtype. 3. Responses to agonists were antagonized to differing extents by the P-1 purinoceptor antagonist 8-phenyltheophylline (10 mu mol/L). 4. In uterine preparations from rats pretreated for 2 days with oestrogen (20 mu g/kg, s,c,) and for 1 day with progesterone (3 mg/animal, s,c,), the inhibitory potencies of adenosine and NECA were reduced, indicating hormonal regulation of uterine responsiveness to P-1 purinoceptor agonists. 5. Stable analogues of ATP caused contractions of unstimulated myometrial preparations from oestrogen-treated animals, indicating activation of a P-2 purinoceptor, possibly of the P-2x subtype, because the relative order of potency was alpha,beta-methylene ATP > beta,gamma-methylene ATP = ATP = 2-methylthioATP.