Regulation of hamster alpha 1B-adrenoceptors expressed in Chinese hamster ovary cells

Eur J Pharmacol. 1996 Mar 28;299(1-3):205-12. doi: 10.1016/0014-2999(95)00838-1.

Abstract

Chinese hamster ovary (CHO) cells were stably transfected to express the hamster alpha 1B-adrenoeceptor, and the function and agonist-induced regulation of the binding properties of these receptors were characterized. The cells expressed approximately 230,000 receptors per cell, with a KD for [3H]prazosin of 140 pM. In assays of competition by epinephrine for [3H]prazosin binding to receptors on intact cells, 88% of the receptors were in a low affinity form. The protein kinase C activator phorbol 12-myristate, 13-acetate (PMA) did not further increase the fraction in the low affinity form, but the protein kinase C inhibitor staurosporine reduced the low affinity fraction to 51%. In sucrose density gradient centrifugation assays of receptor internalization, the percentage of receptors in the light vesicle fraction was 25% for control cells, 53% for epinephrine-pretreated cells, 44% for PMA-pretreated cells, and 53% for cells pretreated with epinephrine plus PMA. Staurosporine completely blocked PMA-induced internalization, but only partially inhibited epinephrine-induced internalization. These results suggest a relationship between low affinity binding and internalization for alpha 1B-adrenoceptors and the involvement of protein kinase C in both processes. Longer-term (24 h) exposure of cells to epinephrine induced an unexpected up-regulation of receptor density of approximately 2-fold that was accompanied by an increase in maximal agonist-stimulated phosphoinositide turnover. These studies document several regulatory differences between alpha 1B-adrenoceptors expressed in transfected CHO cells and those natively expressed in DDT1 MF-2 hamster smooth muscle cells, and they provide additional information on the molecular mechanisms involved in agonist-induced regulation of alpha 1B-adrenoceptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / metabolism
  • Adrenergic alpha-Agonists / pharmacology*
  • Animals
  • CHO Cells / drug effects
  • CHO Cells / metabolism
  • Cricetinae
  • Epinephrine / pharmacology*
  • Phosphatidylinositols / biosynthesis*
  • Prazosin / metabolism
  • Protein Kinase C / metabolism
  • Receptors, Adrenergic, alpha-1 / drug effects*
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Recombinant Proteins / metabolism
  • Staurosporine / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection

Substances

  • Adrenergic alpha-Agonists
  • Phosphatidylinositols
  • Receptors, Adrenergic, alpha-1
  • Recombinant Proteins
  • Protein Kinase C
  • Staurosporine
  • Tetradecanoylphorbol Acetate
  • Prazosin
  • Epinephrine