Ventilatory output and acetylcholine: perturbations in release and muscarinic receptor activation.
Cholinergic transmission may be part of the normal neurochemical processes that support spontaneous ventilation. If this is true, perturbations in acetylcholine (ACh) turnover should alter ventilatory output in a predictable manner. With the use of the isolated perfused brain stem-spinal axis from the neonatal rat, the effects of modifiers of ACh release and blockers of muscarinic receptors on spontaneous C4 (phrenic) output were determined. Vesamicol and cetiedil, inhibitors of ACh release, caused depression and cessation of the C4 output in a dose-dependent manner when added to the perfusate. Muscarinic blockers, particularly M1 and M3 blockers, caused a similar depression. 4-Aminopyridine and tetraethylammonium chloride, facilitators of ACh release, caused stimulation of C4 (phrenic) output. The depressive effects of the blockers and inhibitors were reversible with facilitation of ACh release except in the case of cetiedil. These findings are consistent with the view that the synaptic turnover of endogenous ACh is an important part of the normal neurochemical process that supports and modulates ventilation.
Burton
M D
MD
Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114.
Nouri
K
K
Baichoo
S
S
Samuels-Toyloy
N
N
Kazemi
H
H
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology / Q000502:physiology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010791:Phrenic Nerve / Q000502:physiology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*; D012119:Respiration; D012132:Respiratory Muscles / Q000294:innervation* / Q000378:metabolism
D001381:Azepines; D018680:Cholinergic Antagonists; D018727:Muscarinic Antagonists; D010880:Piperidines; D011976:Receptors, Muscarinic; C006189:vesamicol; C006955:cetiedil; D000109:Acetylcholine