Identification of Beta-Adrenergic Binding Sites in Rabbit Myometrium

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Abstract
Rabbit uterine muscle may contract or relax with adrenergic stimulation depending on the hormonal milicu. This difference in contractile activity is due to alteration of adrenergic response between .alpha.-adrenergic (contraction) and .beta.-adrenergic (relaxation). When rabbits are treated with estrogen followed by progesterone, norepinephrine produces myometrial relaxation. This effect is blocked by propranolol, indicating that it is mediated by .beta. receptor activation. A subcellular preparation of this myometrium has adenylate cyclase activity that can be stimulated by isoproterenol + guanyl-5''-yl-imidodiphosphate (Gpp(NH)p). The radioligand [125I]iodohydroxybenzylpindolol binds to the same preparation. The binding is rapid, 80% maximal in 10 min, and readily reversible (t1/2= 5 min). The binding is high affinity (Kd = 0.12 nM), low capacity (15 fmol[femtomoles]/mg protein), and is to a single class of binding sites. Binding is competed for stereoselectively by .beta. adrenergic agonists and antagonists. The competition of .beta. adrenergic agonists for binding, isoproterenol = ritodrine > epinephrine .mchgt. norepinephrine, is consistent with interactions at a .beta.2-adrenergic receptor.