Inhibition of cholinergic neurotransmission in human airways by beta 2-adrenoceptors.
The purpose of the study was to determine whether catecholamines modulate cholinergic neurotransmission in isolated human airway smooth muscle. Bronchial rings were suspended in organ baths for isometric measurement of tension, and contractions were induced by either electrical field stimulation (EFS) or exogenous acetylcholine (ACh). Isoproterenol, epinephrine, and norepinephrine in that order of potency produced concentration-dependent inhibition of comparable responses to EFS and ACh. However a potency difference of 100-fold for isoproterenol (IC50 = 4.80 X 10(-8) M for EFS and 3.70 X 10(-6) M for ACh) and 10-fold for both epinephrine and norepinephrine was observed for inhibition of responses to EFS compared with responses to ACh. The inhibitory effects of isoproterenol on responses to EFS were prevented by propranolol and ICI 118551 (a beta 2-antagonist) but not by betaxolol (a beta 1-antagonist). Tyramine had no effect on contractions elicited by EFS. These experiments demonstrate that beta-agonists inhibit cholinergic nerve-induced contractions of human bronchi more potently than contractions induced by exogenous ACh, suggesting modulation of cholinergic neurotransmission by prejunctional beta 2-receptors.
Rhoden
K J
KJ
Department of Thoracic Medicine, Brompton Hospital, London, United Kingdom.
Meldrum
L A
LA
Barnes
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology / Q000502:physiology*; D000328:Adult; D000368:Aged; D015784:Betaxolol; D001980:Bronchi / Q000294:innervation*; D002395:Catecholamines / Q000494:pharmacology*; D004558:Electric Stimulation; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation; D009638:Norepinephrine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D009435:Synaptic Transmission
D002395:Catecholamines; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D007545:Isoproterenol; D000109:Acetylcholine; D015784:Betaxolol; D009638:Norepinephrine; D004837:Epinephrine