The mechanism of acetylcholine release from parasympathetic nerves

Abstract

SUMMARY1. The output of acetylcholine from the plexus of the guinea-pig ileum longitudinal strip has been used to study the mechanism of acetylcholine release. From the effects of hexamethonium and tetrodotoxin, it was inferred that 60 % of the normal resting output is due to propagated activity in the plexus, and 40 % to spontaneous release. Tetrodotoxin virtually abolishes the increase in output in response to electrical stimulation.2. Resting acetylcholine output is increased when the bathing medium is changed in the following ways:(a) sodium replacement by sucrose, trometamol or lithium; (b) addition of ouabain or p-hydroxymercuribenzoate (PHMB), or withdrawal of potassium;(c) the combination of PHMB and partial sodium replacement; (d) addition of potassium; this increase in output becomes greater in the absence of sodium.3. The resting output is virtually abolished by calcium withdrawal, and is restored by barium substitution for calcium. It is also reduced by raising the magnesium concentration.4. The enhanced resting output in response to sodium withdrawal also occurs in the absence of calcium.5. Cooling to 5°C greatly reduces both the resting output and the output in response to raised potassium concentration or to electrical stimulation.6. The increase in resting output due to potassium excess is slight up to 25 mm [K+]O, but increases thereafter with about the fourth power of the potassium concentration; it is resistant to tetrodotoxin.

Effects of Anticonvulsant and Convulsant Drugs on the Atpase Activities of Synaptosomes and Their Components

“…Paton et al (1971) and Vizi (1972) (Gilbert & Wylie, 1974a), only the former was sensitive to ethosuximide. In contrast to the other components the vesicles contained no detectable Na+,K+-ATPase activity.…”

“…The suggestion of Paton, Vizi & Zar (1971) that acetylcholine release in the myenteric plexuslongitudinal muscle preparation of the guinea-pig ileum is regulated through inhibition of Na+,K+-ATPase has added new significance to the observations concerning phenytoin action. Recent experiments (Gilbert, Wyllie & Davison, 1975) have provided data supporting this interesting hypothesis but the precise relationships between the activities of the several ATPases of the nerve terminal and transmitter release have yet to be established.…”

Release of noradrenaline from the cat spleen by sodium deprivation

“…The sodium requirement for the retention of catecholamines has been observed in the perfused adrenal gland (Douglas & Rubin, 1961), spleen (Kirpekar & Wakade, 1968a, b), and isolated heart slices (Bogdanski & Brodie, 1969;Keen & Bogdanski, 1970). Similarly, sodium requirement for the retention of acetylcholine has been demonstrated in the myenteric plexus of the guinea-pig ileum (Paton, Vizi & Zar, 1971) and in the motor nerves of the frog sartorius (Birks & Cohen, 1968).…”

Studies of the interaction of 5‐hydroxytryptamine and the perivascular innervation of the guinea‐pig caecum

“…In these experiments hyoscine should have antagonized muscarinic responses to acetylcholine before application of NA. Tetrodotoxin should have eliminated neural activity in the preparations and both tetrodotoxin (Ogura, Mori & Watanabe, 1966;Paton, Vizi & Zar, 1971) and hexamethonium (Paton, Vizi & Zar, 1971) themselves inhibit the release of acetylcholine.…”