[3H]idazoxan binding to the ovine myometrium. Binding characteristics and changes due to steroid hormones

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 253; no. 2; pp. 819 - 824
• Main Authors: Vass-Lopez, A, Garcia-Villar, R, Lafontan, M, Toutain, P L
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.05.1990
• Subjects: Adrenergic alpha-Agonists - pharmacology; Adrenergic alpha-Antagonists - metabolism; Adrenergic alpha-Antagonists - pharmacology; AFFINITY; ANIMALS; AUTONOMIC NERVOUS SYSTEM AGENTS; BASIC BIOLOGICAL SCIENCES; Binding Sites; BIOCHEMICAL REACTION KINETICS; Biological and medical sciences; BODY; CELL CONSTITUENTS; Cell Membrane - drug effects; Cell Membrane - metabolism; CELL MEMBRANES; Dioxanes - metabolism; Dioxins - metabolism; DOMESTIC ANIMALS; DRUGS; ESTRADIOL; ESTRANES; ESTROGENS; Estrogens - pharmacology; Female; FEMALE GENITALS; Fundamental and applied biological sciences. Psychology; GONADS; HORMONES; HYDROGEN COMPOUNDS; HYDROXY COMPOUNDS; Idazoxan; ISOTOPE APPLICATIONS; KETONES; KINETICS; Life Sciences; Mammalian female genital system; MAMMALS; MEMBRANE PROTEINS; MEMBRANES; Morphology. Physiology; Myometrium - drug effects; Myometrium - metabolism; ORGANIC COMPOUNDS; ORGANS; OVARIES; PARASYMPATHOLYTICS; PARASYMPATHOMIMETICS; PREGNANCY; PREGNANES; PROGESTERONE; Progesterone - pharmacology; PROTEINS; REACTION KINETICS; RECEPTORS; Receptors, Adrenergic - drug effects; Receptors, Adrenergic - metabolism; RUMINANTS; SHEEP; STEROID HORMONES; STEROIDS; TRACER TECHNIQUES; Tritium; TRITIUM COMPOUNDS; VERTEBRATES 550201 > Biochemistry > Tracer Techniques; Vertebrates: reproduction; Myometrium; Ovariectomy; Estradiol; Pregnancy; Vertebrata; Mammalia; Alpha blocking agent; Uterus; α-Adrenergic receptor; Female genital system; Sheep; Artiodactyla; Progesterone; Sex steroid hormone; Adrenergic receptor; α2-»Adrenergic receptor; Ungulata
• ISSN: 0022-3565; 1521-0103

[3H]Idazoxan binding to myometrial membranes was investigated in four groups of ewes under different steroid hormone status: control, estradiol-treated and progesterone plus estradiol-treated ovariectomized ewes and pregnant ewes. [3H]Idazoxan binding to myometrial membrane fractions was saturable, reversible, specific and of high affinity. The affinity did not vary significantly between the four groups of ewes (2.8 less than KD less than 4.7 nM). Maximal binding capacity varied significantly among groups: binding of [3H]idazoxan was lower in control ovariectomized ewes than in either estradiol or progestagen plus estrogen-treated ewes (maximal binding capacity, 73 +/- 11 fmol/mg of protein vs. 108 +/- 16 and 318 +/- 65, respectively). The highest [3H]idazoxan binding was measured in pregnant ewes (maximal binding capacity, 1302 +/- 256 fmol/mg of protein). Based on the saturation studies with accurate nonspecific binding definition (phentolamine vs. epinephrine), and on the relative order of potency for selected adrenergic drugs, it could be stated that the binding sites labeled by [3H]idazoxan in our study exhibited most of the alpha-2 adrenoceptor properties. Nevertheless, these alpha-2 adrenoceptors obviously differed from the standard alpha-2A-subtype based on Ki values obtained with yohimbine and prazosin in competition studies of [3H]idazoxan binding. The increase in the number of alpha-2 adrenoceptors under progesterone domination, and especially during gestation, supported the hypothesis that this adrenoceptor subtype could play a major role in the control of the motility pattern of the ovine pregnant uterus.