Bovine pituitary folliculo-stellate cells have beta-adrenergic receptors positively coupled to adenosine 3',5'-cyclic monophosphate production.
The specific beta-adrenergic radioligand [125I]iodocyanopindolol (ICYP) was used to identify and characterize beta-adrenergic receptors in bovine pituitary folliculo-stellate cells (bFSC) grown in culture. Saturation analysis demonstrated the binding of ICYP to bFSC particulate fractions to be of high affinity (apparent Kd = 80 pM) and low capacity (Bmax = 37 fmol/mg protein). The specific beta-adrenergic radioligand [3H] dihydroalprenolol also bound to bFSC particulate preparations with parameters compatible with binding to the beta-adrenergic receptor (Kd = 3.0 nM; Bmax = 52 fmol/mg protein). No specific binding was observed with either the dopamine receptor radioligand [3H]spiperone or the alpha-adrenergic radioligand [3H]dihydro-alpha-ergocryptine. The bFSC beta-adrenergic receptors were further characterized by computer modeling of competition studies with a variety of agonists and antagonists selective for beta-adrenergic subtypes. The pharmacological profiles of ICYP binding obtained from these studies indicated that approximately equal proportions of both beta 1- and beta 2-adrenergic subtypes are expressed in cultured bFSC. Bovine FSC beta-adrenergic receptors are functionally coupled to activation of cAMP. The beta-adrenergic agonists isoproterenol, epinephrine, and norepinephrine provoked a rapid and marked stimulation of intracellular cAMP accumulation. The approximately equipotent effect of epinephrine and norepinephrine indicated that the beta-adrenergic effect on cAMP production is principally mediated via the beta 1-adrenergic receptor. The identification of beta-adrenergic receptors on bFSC positively coupled to adenylate cyclase provides a possible regulatory control pathway for the proposed role of pituitary FSC in the modulation of anterior pituitary hormone secretion.
Findell
P R
PR
Reproductive Endocrinology Center, University of California, San Francisco 94143.
Weiner
R I
RI
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D004983:Ethanolamines / Q000378:metabolism; D020120:Iodocyanopindolol; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D011294:Prenalterol / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D004983:Ethanolamines; D011943:Receptors, Adrenergic, beta; C002904:zinterol; D020120:Iodocyanopindolol; D010869:Pindolol; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007545:Isoproterenol; D011294:Prenalterol; D009638:Norepinephrine; D004837:Epinephrine