Adrenergic Receptors in Inner and Outer Layers of Human Myometrium Near Term: Characterization of Beta-Adrenergic Receptor Sites by [¹²⁵I]-Iodocyanopindolol Binding

Abstract

The Β-adrenergic receptors present in inner and outer layers of human myometrium near term were characterized using the radioiodinated antagonist iodocyanopindolol (ICYP). In both layers ICYP binding is saturable, rapidly reversible, stereoselective, and appears to occur in a single class of sites with a K_D of 30 pmol/l. Adrenergic agonists compete for ICYP binding sites with an order of potency consistent with Β₂-adrenergic potencies: isoproterenol > epinephrine > > norepinephrine. Studies in which CGP 20712 A, a Β₁ adrenergic antagonist, competes for ICYP binding sites in human myometrium reveal that at least 65% of the Β-receptors present are Β₂-subtype, whatever the layer considered. At the 35th week of pregnancy, the density of Β-adrenergic receptors in the inner layer (15.2 fmol/mg of protein) is about 50% higher than in the outer layer. At term, the densities of Β-adrenergic receptors are reduced and exhibit the same values for both layers (5 fmol/mg of protein). These results indicate that the Β-adrenergic receptors in the two layers diminish during pregnancy and reach, at term, an equal and low level of density.

The human near‐term myometrial β3‐adrenoceptor but not the β2‐adrenoceptor is resistant to desensitisation after sustained agonist stimulation

“…Consistent with our previous report where b-AR binding properties were described in human pregnant myometrium (Breuiller et al, 1987), the high-affinity binding site found here resembled that of a b 2 -AR profile. The identity of the low-affinity binding site was confirmed by competition-binding experiments.…”

“…Our results provide strong evidences for resistance of b 3 -AR to the agonist-induced desensitisation in human near-term myometrium. Nevertheless, our binding experiments show that b 3 -AR are more numerous than b 2 -AR in near-term myometrium, while it was admitted that the predominant subtype was the b 2 -AR subtype in this tissue (Hayashida et al, 1982;Breuiller et al, 1987). b 3 -AR have not been previously detected, probably because of insensitive experimental conditions such as unadapted (i.e.…”

“…After a 15 h incubation of myometrial strips with salbutamol or SR 59119A (as described above), crude membranes were obtained as reported previously (Breuiller et al, 1987).…”

In Vitro and in Vivo Pharmacological Characterization of Ethyl-4-{trans-4-[((2S)-2-hydroxy-3-{4-hydroxy-3[(methylsulfonyl)amino]-phenoxy}propyl) Amino]cyclohexyl}benzoate Hydrochloride (SAR150640), a New Potent and Selective Human β3-Adrenoceptor Agonist for the Treatment of Preterm Labor

“…In addition, the myometrial ␤ 3 -adrenoceptor seems to be resistant to agonist-induced desensitization (Rouget et al, 2004). By contrast, ␤ 2 -adrenoceptor expression is either decreased (Breuiller et al, 1987;Chanrachakul et al, 2003) or unchanged (Gsell et al, 2000) at the end of pregnancy, and there is a loss of response to ␤ 2 -mimetics after chronic exposure to these drugs (Berg et al, 1983). This might partly explain the lack of efficacy of ␤ 2 -mimetics at the end of pregnancy.…”

Different α₂-Adrenoceptor Densities in the Circular and Longitudinal Layers of Human Near-Term Myometrium as Revealed by [3H]-Idazoxan Binding Studies

“…Myometrial samples, collected on ice, were dissected free of endometrium and serosa and quickly frozen at -8 0°C . The effectiveness of these procedures, currently performed for other stud ies, were proved by microscopic investigations as pre viously reported [13].…”