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J Appl Physiol (May 2, 2003). doi:10.1152/japplphysiol.00028.2003
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Submitted on January 13, 2003
Accepted on April 23, 2003

Modulation of cholinergic responsiveness through the {beta}-adrenoceptor signal transmission pathway in bovine trachealis

Lorenzo Brichetto1, Pingfang Song1, Emanuele Crimi1, Kai Rehder1, and Vito Brusasco1*

1 Dipartimento di Medicina Interna e Specialita Mediche, Universita' di Genova, Genova, Italy

* To whom correspondence should be addressed. E-mail: Vito.Brusasco{at}unige.it.

The effects of pharmacological stimulation at different levels of the {beta}-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 (10-6M, and 10-5M) and salbutamol (10-7M -10-5M) attenuated significantly both ACh release and contractile force. Forskolin at 10-6M increased significantly ACh release without effect on contractile force, while at 10-5M it increased ACh release but significantly decreased force. Activation of Gs-protein by cholera toxin (10 µg/ml) attenuated significantly both ACh release and contractile force, but its effect on ACh release was abolished by the calcium-activated potassium (KCa) channel blocker, iberiotoxin (10-7M). The KCa-channel opener, NS1619 (10-4M) 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.




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