DESENSITIZATION OF ALPHA-1 ADRENERGIC RECEPTOR-MEDIATED VASCULAR SMOOTH-MUSCLE CONTRACTION

Google Scholar
  • 1 January 1985
    • journal article
    • research article
    • Vol. 234  (1) , 147-152
Abstract
Desensitization of .alpha.-1 receptor-mediated smooth muscle contraction was studied in rabbit aorta. Incubation of rabbit aorta ring segments with epinephrine (10-6 M) for 7 h resulted in a 10-fold loss in sensitivity of the tissue to .alpha.-1 adrenergic receptor-mediated contraction with no change in maximal force of contraction. This loss in sensitivity was specific for .alpha.-1 receptor-mediated contraction because responses to histamine and serotonin were unchanged in these aortas. Prolonged exposure of vessels to histamine (10-5 M) led to desensitization of histamine-mediated contraction without altering responses to .alpha.-1 receptor stimulation. Using [125I]BE2254 [2-[b-4-hydroxyphenyl]ethylaminomethyl]tetralone, a potent .alpha.-1 receptor antagonist, the loss in sensitivity to catecholamines was not mediated by down-regulation of .alpha.-1 receptors nor by a loss in their affinity for epinephrine. Desensitization was associated with a blunting of .alpha.-1 receptor stimulation of phosphatidylinositol turnover. Desensitization of .alpha.-1 receptor-mediated contraction in rabbit aorta does not appear to be mediated by changes in receptor number or affinity but may involve alterations in receptor coupling.