The effects of atropine on [³H]acetylcholine secretion from guinea‐pig myenteric plexus evoked electrically or by high potassium

Abstract

2. With these stimulation parameters, which yielded about the same fractional secretion of [3H]ACh, and with eserine (10 /LM) present in the medium, atropine (1 /M) enhanced the 'indirectly', electrically evoked secretion 3-65 + 034 (n = 6) fold, and that caused by 40 mm or 80 mM-potassium 1-82+0-06 (n = 6) or 1P55+0-09 (n = 10) fold, respectively. Atropine thus enhanced 'indirectly', electrically evoked secretion 4-fold more than that caused by 'direct' depolarization of varicosities with high potassium (P < 0 001).3. This difference is not likely to be caused by depression of the sensitivity of the presynaptic muscarinic receptors to ACh released by nerve stimulation, caused by the hypertonicity of the medium in the potassium stimulation experiments. The medium made hypertonic by addition of Tris-HEPES (80 mM) did lower the binding affinity of membrane preparations of (pre-and post-synaptic) muscarinic receptors, to carbamylcholine, and also the contractile responsiveness of the longitudinal muscle to this agent, in both cases to about one half. But it did not appear to alter the responsiveness of either pre-or post-synaptic muscarinic receptors to endogenous ACh, released by nerve stimulation.4. The results support a dual-mode model for the muscarinic negative feed-back control of ACh secretion from the nerve terminals of this preparation, mainly operating by restriction of the invasion of terminals, and only secondarily by depression of the efficiency of depolarization-secretion coupling in invaded varicosities.5. Since this model has earlier been proposed to apply for the control of secretion of [3H]noradrenaline from the micro-anatomically similar nerve terminals of P. ALBERTS, T. BARTFAI AND L. STJARNE noradrenergic nerves, the present findings suggest that the model may have a wider biological significance, and possibly apply to the control of the secretary activity of bouton8-en-pa88ant nerve terminals in general.

The Leu13‐motilin (KW‐5139)‐evoked release of acetylcholine from enteric neurones in the rabbit duodenum

“…Tetrodotoxin markedly decreased the release of ACh induced by LMT, although a small part of the induced release remained. Since tetrodotoxin prevents neurotransmitter release induced by stimulation of somadendritic regions of the neurone (Vizi et al, 1973), but not by direct depolarization of nerve terminals (Alberts et al, 1982), the main site of action of LMT may be the soma-dendritic region of the enteric cholinergic neurones. Nevertheless, we cannot exclude the possibility that LMT acts on axon terminals of cholinergic neurones or on interneurones connecting with postganglionic cholinergic neurones.…”

Interstitial Cells of Cajal Mediate Cholinergic Neurotransmission from Enteric Motor Neurons

“…Overflow of 14 C was calculated as a fractional release from the tissue. This technique has been used to study the release of ACh from a variety of neuroeffector preparations such as guinea pig GI tissues (Alberts et al, 1982 Solutions and drugs. Muscles were maintained in K RB (37.5 Ϯ 0.5°C), pH 7.3-7.4, containing (in mM): Na ϩ 137.4, K ϩ 5.9, C a 2ϩ 2.5, Mg 2ϩ 1.2, Cl Ϫ 134, HC O 3 Ϫ 15.5, H 2 PO 4 Ϫ 1.2, and dextrose 11.5, bubbled with 97% O 2 and 3% C O 2 .…”

Role of Protein Kinase C in the Vesicular Release of Acetylcholine and Norepinephrine from Enteric Neurons of the Guinea Pig Small Intestine

“…TPA also potentiated the release of ACh and NE evoked by the combination of high K+-depolarization and Ca2+ in the presence of tetrodotoxin; under such conditions, the release of neurotransmitter is induced by the direct depolarization of nerve terminals (21,22), thereby indicating that TPA activated the protein kinase C within the nerve terminals, and the activation of protein kinase C led to the potentiation of the evoked release of neurotransmitters. TPA-induced potentiation of the evoked release of ACh and N E was greater at a low concentration of external Ca2+ than at the high concentration, which is in agreement with the case of ACh release from the caudate slices (6) and NE release from the sinus node (7).…”