The search for prejunctional inhibitory muscarinic receptors in human bronchus.
The purpose of our study was to search for and classify prejunctional inhibitory muscarinic receptors in human bronchus with a wide range of muscarinic antagonists. Human bronchial airway smooth muscle strips, collected at thoracotomy from 54 subjects, 31 patients with chronic airway obstruction and 23 control subjects, were suspended in organ baths and stimulated by electrical field stimulation. The stimulation parameters were: frequency: 32 Hz; Grass reading voltage: 70 V (voltage between the electrodes: 15 V); pulse duration: 0.5 msec and train duration: 10 sec, every minute. Twitch responses of smooth muscle strips of 27 subjects (14 with and 13 without chronic airway obstruction) were sufficiently stable to search for the effects of M1-, M2- and M3-selective antagonists. All antagonists were added to the bath in a cumulative manner and decreased twitch contraction. No convincing evidence was found for the presence of prejunctional inhibitory muscarinic receptors of the M2-subtype, reasons for this obvious absence are discussed. Anaesthetical drugs for example, may mask the prejunctional inhibitory muscarinic receptors. The question remains whether the used electrical field stimulation experiments are suitable to point out prejunctional inhibitory muscarinic receptors. It is concluded that additional experiments with other experimental methods and in patients with different anaesthetical treatment are needed.
Nagtegaal
J E
JE
Department of Pharmacology, University of Nijmegen, The Netherlands.
Lammers
J W
JW
Rodrigues de Miranda
J F
JF
Gribnau
F W
FW
D000402:Airway Obstruction / Q000378:metabolism / Q000503:physiopathology; D001980:Bronchi / Q000378:metabolism* / Q000502:physiology; D002908:Chronic Disease; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009116:Muscarine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018727:Muscarinic Antagonists; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism* / Q000502:physiology
D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D009116:Muscarine