EVIDENCE FOR 2 SUBTYPES OF ALPHA-ADRENERGIC RECEPTORS IN CANINE AIRWAY SMOOTH-MUSCLE

Abstract

The contractile response of canine tracheal muscle to i.a. [intraarterial] phenylephrine, clonidine and norepinephrine [NE] was studied isometrically in situ in 32 dogs after .beta.-adrenergic and ganglionic blockade. I.a. phenylephrine caused dose-related tracheal contraction which was not altered by yohimbine (5 .mu.g/kg i.a.). Prazosin (4 mg/kg i.v.) caused a 77 .+-. 3% decrease in tracheal response to i.a. phenylephrine. Clonidine caused dose-related tracheal contraction, which was not altered by prazosin (4 mg/kg i.v.) but was 95 .+-. 2% blocked by 5 .mu.g/kg i.a. of yohimbine. NE caused tracheal muscle contraction which was greater than both phenylephrine (P < 0.05) and yohimbine (P < 0.001). Prazosin (4 mg/kg i.v.) caused 53 .+-. 6% blockade and yohimbine (5 .mu.g/kg i.a.) caused 76 .+-. 2% blockade of the response to i.a. NE; prazosin plus yohimbine caused > 98% blockade of the response to i.a. NE. The dose-response curve to i.a. acetylcholine was not altered by treatment with prazosin (4 mg/kg i.v.) plus yohimbine (5 .mu.g/kg i.a.). Tracheal contraction induced by sympathomimetic amines is mediated by 2 subtypes of .alpha.-adrenergic receptors on tracheal muscle, .alpha.-1 for phenylephrine, .alpha.-2 for clonidine and both .alpha.-1 and .alpha.-2 for NE.