Desensitization of beta-adrenoreceptors in guinea-pig trachea: a prostaglandin mediated phenomenon.

1 The formation and release of PGE2-like material (PGE2-lm) from guinea-pig isolated trachea and human bronchi following relaxation with isoprenaline (I) was investigated. 2 When airway smooth muscle precontracted with pilocarpine is relaxed by I, PGE2-lm is released in the bathing fluid. Under conditions of beta-adrenoreceptor desensitization, a greater amount of PGE2-lm is formed and the responsiveness of guinea-pig tracheal spirals to cumulative doses of I is diminished. 3 Inhibition of cyclo-oxygenase with indomethacin does not modify the relaxation induced by I but prevents the occurrence of refractoriness to I as well as formation and release of PGE2-lm. Addition of exogenous PGE2 to guinea-pig tracheas which were treated with indomethacin is able to restore the capacity of I to cause tachyphylaxis. 4 It is concluded that PGE2 which does not mediate the relaxation induced by I in airway smooth muscle, is responsible for the onset of desensitization of the beta-adrenoreceptor.