Modulation of cholinergic responsiveness through the [beta]-adrenoceptor signal transmission pathway in bovine trachealis.
The effects of pharmacological stimulation at different levels of the beta-adrenoceptor (AR) pathway, including the receptor, the receptor-coupled Gs protein, and adenylyl cyclase, were studied by simultaneous measurements of acetylcholine (ACh) release and isometric force evoked by electric stimulation in isolated bovine trachealis. The beta-AR agonists isoproterenol (10-6 and 10-5 M) and salbutamol (10-7 to 10-5 M) significantly attenuated both ACh release and contractile force. Forskolin, at 10-6 M, significantly increased ACh release without effect on contractile force, whereas at 10-5 M it increased ACh release but significantly decreased force. Activation of Gs protein by cholera toxin (10 microg/ml) significantly attenuated both ACh release and contractile force, but its effect on ACh release was abolished by calcium-activated potassium (KCa)-channel blocker iberiotoxin (10-7 M). The KCa-channel opener NS-1619 (10-4 M) attenuated significantly both ACh release and contractile force. It is concluded that beta-AR agonists attenuate cholinergic neurotransmission in isolated bovine trachealis model by a mechanism not involving cAMP but KCa channels.
Dipartimento di Medicina Interna e Specialitá Mediche, Università di Genova, 16132 Genova, Italy.
Lorenzo
L
Brichetto
Pingfang
P
Song
Emanuele
E
Crimi
Kai
K
Rehder
Vito
V
Brusasco
D000109:Acetylcholine / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004558:Electric Stimulation; D007545:Isoproterenol / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D010455:Peptides; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; C064719:iberiotoxin; D002772:Cholera Toxin; D007545:Isoproterenol; D000109:Acetylcholine; D000420:Albuterol