title: Characterization of alpha-2 adrenergic receptors in the OK cell, an opossum kidney cell line.
abstract: We have characterized alpha-2 adrenergic receptors in OK cells, an opossum kidney-derived cell line. In membrane saturation binding experiments, [3H]rauwolscine (Kd = 74 pM) was 3-fold more potent than [3H]yohimbine (Kd = 230 pM). Each labeled a single class of binding sites with densities of 135 and 124 fmol/mg of protein for [3H]rauwolscine and [3H]yohimbine, respectively. Inhibition of [3H]rauwolscine and [3H]yohimbine binding by several alpha adrenergic agonists and antagonists demonstrated the radioligands labeled an alpha-2 type adrenergic receptor with a pharmacological profile similar to the alpha-2B receptor subtype. The rank order of potency for antagonist inhibition of binding was yohimbine greater than prazosin = phentolamine greater than chlorpromazine = corynanthine, whereas the rank order of agonist potency was oxymetazoline = clonidine greater than or equal to UK-14,304 greater than or equal to (-)-epinephrine greater than (-)-norepinephrine. The oxymetazoline, clonidine and antagonist inhibition curves were routinely monophasic and modeled best as a single class of binding sites. For the other agonists, inhibition binding curves were biphasic with approximately 35% of the binding sites existing in a high affinity state. These curves were shifted to the right in the presence of 0.1 mM GTP, and in general modeled as a single class of binding sites. UK-14,304, (-)-epinephrine, (-)-norepinephrine and oxymetazoline attenuated parathyroid hormone-stimulated cyclic AMP production by up to 70% in whole cell monolayers in a dose-dependent manner via a pertussis toxin-sensitive mechanism. With the exception of oxymetazoline, this inhibition could be reversed with alpha adrenergic antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000068438:Brimonidine Tartrate; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D007668:Kidney / Q000032:analysis*; D007700:Kinetics; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology; D011810:Quinoxalines / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000032:analysis*; D015016:Yohimbine / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010281:Parathyroid Hormone; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D000068438:Brimonidine Tartrate; D000242:Cyclic AMP