RT Journal Article
SR Electronic
T1 Mechanism of the bradycardia produced in the cat by the anticholinesterase neostigmine.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 194
OP 200
VO 265
IS 1
A1 S B Backman
A1 M Bachoo
A1 C Polosa
YR 1993
UL http://jpet.aspetjournals.org/content/265/1/194.abstract
AB Neostigmine evoked bradycardia in vagotomized, propranolol-treated cats. Heart rate decreased by 50% with 0.4 +/- 0.2 mg/kg (mean +/- S.D.) i.v. of neostigmine. The bradycardia was attenuated after acetylcholine (ACh) depletion in the cardiac parasympathetic pathway suggesting ACh release within this pathway was involved. The bradycardia was unchanged after preganglionic terminal degeneration suggesting ACh release was from cardiac ganglion cells. Edrophonium produced a much weaker bradycardia suggesting the anticholinesterase effect of neostigmine may not produce the bradycardia. The neostigmine-induced bradycardia was blocked by systemic atropine (ED50, 0.005 +/- 0.001 mg/kg), pancuronium bromide (ED50, 0.033 +/- 0.021 mg/kg), pirenzepine (ED50, 74.7 +/- 7.9 micrograms/kg), hexamethonium (ED50, 8.3 +/- 1.6 mg/kg) and d-tubocurarine (ED50, 8.6 +/- 3.0 micrograms/kg). The doses of hexamethonium and d-tubocurarine that blocked the neostigmine-induced bradycardia were significantly higher than required for blocking the bradycardia produced by vagus nerve stimulation. Hexamethonium (60 mg/kg i.v.) had no effect on the bradycardia produced by the muscarinic agonist methacholine (100-300 micrograms/kg/min i.v.). The dose of pirenzepine that blocked the neostigmine-induced bradycardia was lower than required for blocking the bradycardia produced by vagus nerve stimulation. McN-A-343 ([4-hydroxy-2-butynyl]-1-trimethyl ammonium m-chlorocarbanilate chloride) (1 mg/kg i.v.) did not produce bradycardia. These observations suggest neostigmine evokes bradycardia by activation of ACh receptors on cardiac ganglion cells producing ACh release and activation of cardiac M2 receptors. The low sensitivity of the neostigmine-induced bradycardia to pirenzepine, and the failure of McN-A-343 to evoke bradycardia, suggest the receptor on cardiac ganglion cells is not an M1-type.(ABSTRACT TRUNCATED AT 250 WORDS)