Specificity of the beta 2-adrenergic receptor stimulating cyclic AMP accumulation in the intermediate lobe of rat pituitary gland

Eur J Pharmacol. 1982 Jul 16;81(3):411-20. doi: 10.1016/0014-2999(82)90106-6.

Abstract

Changes of cyclic AMP levels were used to assess the specificity of the beta-adrenergic receptor in primary cultures of cells prepared from the intermediate lobe of rat pituitary gland. During a 4 min incubation, beta-adrenergic agonists led to a 4 to 6 fold stimulation of cyclic AMP concentration with the following order of potency (Kd values): zinterol (0.75 nM) greater than hydroxybenzylisoproterenol (1.0 nM) greater than (--)-isoproterenol (4.6 nM) greater than soterenol greater than (7.7 nM) greater than (--)-epinephrine (10 nM) greater than OPC 2009 (procaterol, 11 nM) much greater than (--)-norepinephrine (300 nM). The potent antagonists cyanopindolol, (--)-propranolol and hydroxybenzylpindolol reversed the stimulatory effect of (--)-isoproterenol at Kd values of 0.4-0.6 nM. Other beta-adrenergic antagonists had the following order of potency: pindolol = (--)-alprenolol = timolol (0.9-1.0 mM) much greater than metoprolol (100 nM) greater than dichloroisoproterenol (300 nM) greater than butoxamine (1100 nM). The beta 1-selective antagonist practolol had a low potency at 700 nM. The stereoselectivity of the receptor is indicated by the 400 to 70 fold higher potency of the (--)-isomers of isoproterenol, epinephrine and propranolol as compared to their (+)-stereoisomers. The data show that the beta-adrenergic receptor in the intermediate lobe of the rat pituitary gland is mainly of the bet 2-subtype. Study of this pure population of postsynaptic beta-adrenergic receptors where binding could be correlated with other parameters of cellular activity (cyclic AMP formation and alpha-MSH secretion) should yield useful information about the less accessible adrenergic systems of the brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP / metabolism*
  • Epinephrine / pharmacology
  • Female
  • Isoproterenol / pharmacology
  • Melanocyte-Stimulating Hormones / blood
  • Norepinephrine / pharmacology
  • Pituitary Gland / metabolism*
  • Propranolol / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Receptors, Adrenergic / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Time Factors

Substances

  • Receptors, Adrenergic
  • Receptors, Adrenergic, beta
  • Melanocyte-Stimulating Hormones
  • Propranolol
  • Cyclic AMP
  • Isoproterenol
  • Norepinephrine
  • Epinephrine