CHARACTERIZATION OF THE ADRENORECEPTOR ACTIVITIES OF ISOPRENALINE IN THE FIELD STIMULATED RAT VAS DEFERENS: SELECTIVE SUPERSENSITIVITY TO β2-MEDIATED RESPONSES FOLLOWING RESERPINE TREATMENT

1 Low concentrations of isoprenaline (EC₅₀= 45.6 nM) inhibited contractions in the isolated field stimulated rat vas deferens. This inhibitory effect was markedly attenuated by the postjunctional β₂-adreno-receptor antagonist timolol, but not affected by the prejunctional α₂ or postjunctional α₁-adrenoreceptor antagonists rauwolscine and prazosin, respectively. 2 In vas deferens of rats previously treated with reserpine, the postjunctional β₂-adrenoreceptor-mediated inhibitory response to isoprenaline was markedly potentiated. 3 High concentrations of isoprenaline (EC₅₀= 1.5 uM) also inhibited contractility in tissues in which postjunctional β₂-adrenoreceptors were maximally blocked by high concentrations of timolol. This contractile inhibition produced by isoprenaline was abolished by rauwolscine but not significantly altered by prazosin or pretreatment of the rats with reserpine indicating stimulation of prejunctional α₂-adreno-receptors. 4 Rauwolscine pretreatment unmasked an ability of isoprenaline (EC₅₀= 17.1 juM) to produce enhancement of field stimulation-induced contractions. This response was abolished by prazosin but was unaffected by timolol or reserpinization indicating an action upon postjunctional α₁-adrenoreceptors. 5 The data indicate isoprenaline activates adrenoreceptor mechanisms in the field stimulated rat vas deferens by a direct action not dependent upon endogenous catecholamines and with an order of activity of β₂>α₂>α₁. Pretreatment with reserpine produces rapid and selective development of supersensitivity to the postjunctional β₂-mediated inhibitory response of isoprenaline in this preparation.