Ritodrine: A β-adrenergic receptor antagonist in human amnion

Abstract

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. 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. 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. 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.