Desensitization of the alpha adrenergic receptor system in guinea pig vas deferens

Desensitization induced by alpha adrenergic (alpha-Ad) stimulation was investigated in organ cultured vas deferens of guinea pig. Brief exposure (1-2 min) of the muscle to noradrenaline (NA) caused short-term desensitization to both NA and acetylcholine (ACh), but not to high K+. After removing the agonist this desensitization completely disappeared within 15 min. Prolonged exposure to NA (i.e., cultured with NA for 3-24 hr) elicited long-term desensitization to NA, ACh and K+ (50 mM), but it did not change the maximal contraction by high K+ (154 mM). After removing NA from the culture medium the response to the agonist was restored to normal within 24 hr, but not within 15 min. The number and affinity of alpha-Ad and muscarinic ACh receptors, which were measured by the binding of 3H-WB4101 and 3H-QNB, respectively, were not changed in the muscle during these treatments. Moreover, long-term desensitization, but not short-term desensitization, was depressed by the concomitant presence of cycloheximide. The possible mechanisms of desensitization were discussed in comparison with those of various receptor systems.