Role of alpha-adrenergic receptors in cartilaginous and non-cartilaginous human airways.
An imbalance between the density of alpha- and beta-adrenergic receptors in airway smooth muscle has been suggested as one of the potential underlying mechanisms of bronchial asthma. Therefore, the present study was conducted to examine the presence and functional behavior of alpha-adrenoceptors in isolated human bronchi and bronchioles. Human airway tissues did not show any spontaneous tone during equilibration in physiological solution. Sensitivity of non-cartilaginous airways (8th generation and smaller) to histamine was approximately 3 times more than cartilaginous (2nd-7th generation) airways. In the presence of beta-adrenoceptor blockade, norepinephrine (3 X 10(-4) M) evoked approximately 14-40% of maximum histamine contraction in cartilaginous and non-cartilaginous airways from three donors. When tone in these tissues was elevated by pretreatment with histamine (10(-5) M), leukotriene D4 (10(-10) M), carbachol (1 X 10(-6) M-3 X 10(-6) M) or KCl (10(-2) M), the sensitivity to norepinephrine was potentiated. Airway tissue from one donor was found to be highly reactive to norepinephrine and the maximum contractions were 118 and 145% of maximum histamine contraction for cartilaginous and non-cartilaginous airways, respectively. Time to reach maximum contraction in cartilaginous airways was 80 min compared to 21 min for non-cartilaginous airways from the same donor. These data suggest that human airways contain contractile alpha-adrenoceptors in addition to relaxant beta-adrenoceptors, which haven been reported previously in the literature. Though activation of alpha-adrenoceptors induces contractions in human airway smooth muscle, the potency of norepinephrine for alpha-adrenoceptors in these airways is low compared to that reported for vascular smooth muscle.
D000328:Adult; D000403:Airway Resistance / Q000187:drug effects*; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D002356:Cartilage / Q000502:physiology; D002648:Child; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000502:physiology*; D012137:Respiratory System / Q000294:innervation*
D011942:Receptors, Adrenergic, alpha; D009638:Norepinephrine