Ritodrine: a beta-adrenergic receptor antagonist in human amnion.
OBJECTIVE
Human amnion is important in the initiation of labor. Ritodrine, when administered as a tocolytic, is found unchanged in amniotic fluid. We characterized effects of ritodrine binding to beta-adrenergic receptors in amnion and amniocytes.


METHODS
Iodine 125-iodopindolol, beta-adrenergic receptor agonists, and beta-adrenergic receptor antagonists were used to describe binding characteristics. Experiments were designed with and without isoproterenol and ritodrine to study intracellular cyclic adenosine 3'5'-monophosphate and prostaglandin E2 release.


RESULTS
Scatchard analysis revealed a single class of saturable binding sites, with maximum binding capacity of 70.0 +/- 17.2 fmol/mg protein (n = 12) and with high-affinity dissociation constant of 458.9 +/- 72.1 pmol/L. Agonists and antagonists competed for the 125I-iodopindolol binding site consistent with a beta 2-adrenergic receptor. Hill coefficients were 0.6 to 0.8 for agonist competition and 1.0 for antagonist competition and ritodrine. Stimulation with isoproterenol resulted in dose-dependent increases in cyclic adenosine 3'5'-monophosphate and prostaglandin E2. Ritodrine failed to stimulate cyclic adenosine 3'5'-monophosphate and inhibited isoproterenol-stimulated cyclic adenosine 3'5'-monophosphate and prostaglandin E2 production.


CONCLUSIONS
In human amnion binding of ritodrine to beta 2-adrenergic receptors and lack of ritodrine-mediated postreceptor effects are characteristic of a beta 2-adrenergic antagonist.
Collins
P L
PL
Department of Obstetrics and Gynecology, University of California, San Francisco.
Zink
E
E
Moore
R M
RM
Roberts
J M
JM
Maguire
M E
ME
Moore
J J
JJ
D000650:Amnion / Q000378:metabolism*; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000096:biosynthesis; D004837:Epinephrine / Q000378:metabolism; D006801:Humans; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012312:Ritodrine / Q000378:metabolism* / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; C029247:3-iodopindolol; D010869:Pindolol; D000242:Cyclic AMP; D012312:Ritodrine; D015232:Dinoprostone; D007545:Isoproterenol; D009638:Norepinephrine; D004837:Epinephrine