ABSTRACT
The effect of muscarinic antagonists was studied on the muscarinic slow IPSP (inhibitory postsynaptic potential) and slow EPSP (excitatory postsynaptic potential) in bullfrog sympathetic ganglia using the sucrose-gap recording method. Pirenzepine, alcuronium and atropine reduced slow IPSP amplitude more than slow EPSP amplitude. The most selective antagonists studied were pancuronium and gallamine which blocked or substantially reduced the slow IPSP without significantly affecting slow EPSP amplitude. The results suggest that the muscarinic inhibitory response may involve a different muscarinic receptor subtype, and/or receptor-ion-channel complex, than the muscarinic excitatory response.
Subject(s)
Ganglia, Sympathetic/physiology , Receptors, Muscarinic/physiology , Alcuronium/pharmacology , Animals , Atropine/pharmacology , Electric Stimulation , Evoked Potentials/drug effects , Gallamine Triethiodide/pharmacology , Ganglia, Sympathetic/drug effects , In Vitro Techniques , Pancuronium/pharmacology , Pirenzepine/pharmacology , Rana catesbeiana , Receptors, Muscarinic/drug effectsABSTRACT
The effect of various non-depolarizing neuromuscular blocking agents (gallamine, pancuronium, vecuronium, d-tubocurarine, metocurine, atracurium and pipecuronium) on [3H]acetylcholine release in the response to field electrical stimulation was investigated in vitro in preparations of the guinea pig right atrium. In this preparation, atropine enhanced and oxotremorine, a muscarinic agonist, reduced the release of [3H] acetylcholine. Atropine reversed the inhibitory effect of oxotremorine in a concentration dependent manner, indicating that there is negative feedback modulation of acetylcholine release from the vagal nerve. While pancuronium, gallamine and atracurium enhanced the release of [3H]acetylcholine, d-tubocurarine, metocurine, vecuronium and pipecuronium did not affect it. Pancuronium and gallamine also reduced the inhibitory effect of oxotremorine and the Kd value of pancuronium for muscarinic receptors located on cholinergic nerve terminals was 2.31 microM. These findings indicate that pancuronium and gallamine enhanced the release of acetylcholine from the atrial parasympathetic nerve, probably by inhibiting presynaptic muscarinic receptors.
Subject(s)
Acetylcholine/metabolism , Heart Atria/metabolism , Neuromuscular Nondepolarizing Agents/pharmacology , Animals , Atracurium/pharmacology , Atrial Function, Right/physiology , Electric Stimulation , Female , Gallamine Triethiodide/pharmacology , Guinea Pigs , Heart Atria/drug effects , In Vitro Techniques , Male , Pancuronium/pharmacology , Parasympathetic Nervous System/physiology , Pipecuronium/pharmacology , Receptors, Muscarinic/physiology , Tubocurarine/analogs & derivatives , Tubocurarine/pharmacology , Vecuronium Bromide/pharmacologyABSTRACT
1. The interaction of some neuromuscular blocking drugs such as gallamine, pancuronium and stercuronium with muscarinic receptors has several features which distinguish these compounds from competitive antagonists in functional and binding studies. 2. They also differentiate between muscarinic receptors and may produce effects on ion channels.