DESENSITIZATION OF β-ADRENORECEPTORS IN GUINEA-PIG TRACHEA: A PROSTAGLANDIN MEDIATED PHENOMENON

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Abstract
The formation and release of PG[prostaglandin]E2-like material (PGE2-lm) from guinea pig isolated trachea and human bronchi following relaxation with isoprenaline (I) was investigated. 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. Inhibition of cyclooxygenase 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. Apparently, 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.