Beta-adrenoceptor desensitization in guinea-pig isolated trachea

Eur J Pharmacol. 1988 Nov 22;157(2-3):135-45. doi: 10.1016/0014-2999(88)90376-7.

Abstract

Exposure to (-)-isoprenaline (25 microM, 1 h) caused a stereoselective, time and concentration-related decrease in smooth muscle beta 2-adrenoceptor function in guinea-pig trachea. Furthermore, tracheal relaxant responsiveness to the beta-adrenoceptor agonists (+/-)-fenoterol and (-)-noradrenaline was reduced, while that to theophylline and nitroprusside was unaffected. Responsiveness to forskolin was marginally but significantly reduced. Indomethacin, a cyclooxygenase inhibitor and mepacrine, an inhibitor of phospholipid turnover, had no significant effect on the extent of isoprenaline-induced desensitization. Conversely, cortisol (25 microM) significantly reduced desensitization and enhanced the rate of spontaneous recovery of responsiveness to isoprenaline. Desensitization was not accompanied by a reduction in the density of beta-adrenoceptors in the trachea, as assessed by binding and light microscopic autoradiography using [125I]iodocyanopindolol [( 125I]CYP). Thus, desensitization was probably caused primarily by beta-adrenoceptor/adenyl cyclase uncoupling. This model may be useful in investigations of the effect of glucocorticoids on the beta-adrenoceptor dysfunction recognized in severe asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoradiography
  • Carbachol / pharmacology
  • Female
  • Fenoterol / pharmacology
  • Guinea Pigs
  • Hydrocortisone / pharmacology
  • In Vitro Techniques
  • Indomethacin / pharmacology
  • Isoproterenol / pharmacology
  • Male
  • Muscle Relaxation / drug effects
  • Norepinephrine / pharmacology
  • Quinacrine / pharmacology
  • Receptors, Adrenergic, beta / drug effects*
  • Theophylline / pharmacology
  • Trachea / drug effects*

Substances

  • Receptors, Adrenergic, beta
  • Fenoterol
  • Carbachol
  • Theophylline
  • Quinacrine
  • Isoproterenol
  • Hydrocortisone
  • Norepinephrine
  • Indomethacin