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A 1 ‐and A 2 ‐PURINOCEPTORS IN THE GUINEA‐PIG UTERUS
Author(s) -
Haynes John M.,
Pennefather Jocelyn N.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01642.x
Subject(s) - myometrium , endometrium , endocrinology , medicine , uterus , adenosine , dissociation constant , chemistry , cgs 21680 , agonist , biology , receptor , adenosine receptor
SUMMARY 1. Radioligand binding and functional studies were undertaken to investigate the P 1 ‐purinoceptors present in the separated myometrial layers and the endometrium of the guinea‐pig uterus. 2. In preparations of endometrium‐denuded circular myometrium, the A 2 ‐selective agonists (2‐ p ‐(2‐carboxyethyl)phenethylamino‐5'‐ N ‐ethylcarboxamido‐adenosine (CGS 21680, 100 μmol/L) and N ‐ethylcarboxamido adenosine (NECA, 1–10 μmol/L) inhibited contractile responses to phenylephrine. In preparations of endometrium‐intact circular myometrium, NECA (10 μmol/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 [ 3 H]‐NECA binding sites. The mean maximal densities of binding sites ( B max ) were 2.08, 14.7 and 15.5 fmol/mg protein, and p K D (neg. log dissociation constant) values were 9.82, 9.19 and 7.44, respectively. 4. (R‐) and (S‐) ‐ N 6 ‐(2‐phenylisopropyl)adenosine (R‐ and S‐PIA) both competed for two [ 3 H]‐NECA binding sites in preparations of circular myometrium. CGS 21680 competed for two [ 3 H]‐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 ≥ R‐PIA ≥ CGS 21680 (circular myometrium), R‐PIA ≥ CGS 21680 ≥ S‐PIA (longitudinal myometrium) and CGS 21680 > > S‐PIA ≥ R‐PIA (endometrium). 5. In preparations of circular myometrium, longitudinal myometrium and endometrium the selective A 1 ‐purinoceptor antagonist, 1,3‐dipropyl‐8‐(2‐amino‐4‐chloro)‐phenylxanthine (PACPX), competed for two [ 3 H]‐NECA binding sites, the non‐selective antagonist 3,7‐dimethyl‐1‐propargylxanthine (DMPX), competed for one site only. 6. NECA increased cyclic adenosine monophosphate (CAMP) levels in preparations of both circular myometrium and endometrium. 7. These results indicate that P 1 ‐purinoceptors of the A 2 ‐subtype mediate the inhibitory effects of adenosine analogues on the phenylephrine‐induced contractions of the circular myometrium of the guinea‐pig, this effect is modified by the presence of the endometrium. There is no evidence that the [ 3 H]‐NECA binding sites of the longitudinal myometrium correlate with functional P 1 ‐purinoceptors in this tissue.