Influence of steroid hormone treatments or pregnancy on [3H]prazosin and [3H]rauwolscine binding to myometrial alpha-adrenoceptors in the ewe.
The adrenergic antagonists [3H]prazosin and [3H] rauwolscine were used to identify alpha 1- and alpha 2-adrenoceptors respectively in the ovine myometrium. Ewes were allocated to four groups according to steroid hormone treatments or physiological status, namely ovariectomized ewes either as untreated controls, treated with oestradiol-17 beta or progestagen plus oestradiol-17 beta, and pregnant ewes at mid-gestation. Binding of both [3H]prazosin and [3H]rauwolscine to membrane preparations from the ovine myometrium was saturable, of high affinity and rapidly reversed by phentolamine (10 mumol/l). Based on the relative order of potency of selected adrenergic agonists and antagonists, the myometrial binding sites labelled by [3H]prazosin and [3H]rauwolscine were characterized as alpha 1- and alpha 2-adrenoceptors respectively. Saturation binding studies with [3H]prazosin showed that the number of alpha 1-adrenoceptors was low (maximal binding capacity, Bmax, between 19 and 24 fmol/mg protein) and there were no noticeable differences between the animal groups. Moreover, the equilibrium dissociation constant (Kd) did not vary significantly between groups (Kd between 0.10 and 0.17 nmol/l). In contrast, saturation binding studies with [3H]rauwolscine revealed the presence of a high number of alpha 2-adrenoceptors. Values of Bmax were far higher in the pregnant ewes (1096 +/- 241 fmol/mg protein; means +/- S.D.) than in any of the non-pregnant ovariectomized ewes. For these latter groups, the highest Bmax values were found in the group treated with both progestagen and oestrogen (382 +/- 77 fmol/mg protein) compared with treatment with oestrogen alone (101 +/- 8 fmol/mg protein) or with controls (82 +/- 12 fmol/mg protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Vass-Lopez
A
A
INRA Pharmacology-Toxicology Station, Toulouse, France.
Garcia-Villar
R
R
Lafontan
M
M
Toutain
P L
PL
D000317:Adrenergic alpha-Antagonists / Q000378:metabolism*; D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D003425:Flurogestone Acetate / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D007700:Kinetics; D009215:Myometrium / Q000378:metabolism*; D010052:Ovariectomy; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D012756:Sheep / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D012739:Gonadal Steroid Hormones; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D004958:Estradiol; D003425:Flurogestone Acetate; D011224:Prazosin; D010646:Phentolamine