title: Effect of mesulergine on prolactin secretion and dopamine D2 receptors-adaptive changes in diethylstilbestrol-induced hyperplasia of the rat anterior pituitary.
abstract: Mesulergine (N,N-dimethylsulphamide-N'-1,6-dimethyl-ergoline-8 alpha-yl) is an active semisynthetic ergot derivative with lower antiprolactin potency compared with bromocriptine or pergolide. Since no data are yet available on the effects of mesulergine on pituitary dopamine receptors, the present study has been designated to elucidate the influence of this drug on prolactin secretion in vivo and in vitro and 3H-spiperone binding by the anterior pituitary gland in female Wistar rats with experimentally induced hyperprolactinemia. Three weeks after bilateral ovariectomy and subcutaneous implantation of silastic tubes, containing 10 mg of diethylstilbestrol, a dramatic rise in serum prolactin levels was observed (1.67 +/- 0.23 vs. 80.82 +/- 3.80 ng/ml; P less than 0.001). Mesulergine attenuated the stimulatory effect of diethylstilbestrol on serum prolactin level in a time- and dose-dependent fashion. At concentration range between 10(-5) and 10(-7) M it also inhibited prolactin secretion from cultured rat pituitary cells to the medium during 180 min incubation in a dose-dependent manner. Scatchard analyses performed on the in vitro 3H-spiperone binding kinetics in a dispersed anterior pituitary cell culture, prepared from the pituitaries from rats treated for four weeks with diethylstilbestrol, showed that chronic mesulergine treatment (in dose of 3.0 mg/kg injected s.c. for 10 days) induced a significant decrease in the number of dopamine D2-binding sites (Bmax 28.00 +/- 4.20 vs. 42.80 +/- 4.76 fmol/10(6) cells; P less than 0.01) without any changes in D2-receptor affinity. Our results suggested that antiprolactin activity of mesulergine in vivo and in vitro is probably associated with agonistic effect of this drug on D2-dopamine receptors.
authors.affiliation: Institute of Endocrinology, Medical Academy of Lodz, Poland.
authors.forename: H
authors.initials: H
authors.lastname: Pisarek
authors.forename: H
authors.initials: H
authors.lastname: Stepien
authors.forename: M
authors.initials: M
authors.lastname: Pawlikowski
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology*; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D006966:Hyperprolactinemia / Q000139:chemically induced; D010479:Pergolide / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D011388:Prolactin / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
chemical_list: D000978:Antiparkinson Agents; D004873:Ergolines; D017448:Receptors, Dopamine D2; D014316:Tritium; D010479:Pergolide; D001971:Bromocriptine; D013134:Spiperone; D004054:Diethylstilbestrol; D011388:Prolactin; C031649:mesulergine