Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum

Kilbinger, H.; Wessler, Ignaz

doi:10.1007/bf00498547

Cited by 52 publications

(16 citation statements)

References 19 publications

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“…Since the affinity of muscarinic receptors for carbamylcholine is closely similar to that for ACh (Heilbronn & Bartfai, 1978;Kilbinger & Wessler, 1980b), both of these observations indicate that hypertonicity does interfere with stimulation of muscarinic receptors, at least when tissues are exposed to exogenous agonist at low micromolar concentrations.…”

Section: P Alberts T Bartfai and L Stjarne Discussionmentioning

confidence: 83%

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

Alberts

Bartfai

Stjärne

1982

The Journal of Physiology

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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.

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Section: P Alberts T Bartfai and L Stjarne Discussionmentioning

confidence: 83%

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

Alberts

Bartfai

Stjärne

1982

The Journal of Physiology

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“…Muscarinic receptors with an inhibitory function are known to exist in the parasympathetic ganglia of cat bladder (Gallagher etal., 1982) and in parasympathetic nerve terminals in guinea-pig ileum (Kilbinger & Wessler, 1980;Fosbraey & Johnson, 1980) although gallamine has not been tested on these receptors. Our results with gallamine can be explained by blockade of inhibitory muscarinic receptors located in the pulmonary parasympathetic cholinergic nerves.…”

Section: Discussionmentioning

confidence: 99%

Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Fryer¹,

Maclagan²

1984

British J Pharmacology

300

207

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1 In anaesthetized guinea-pigs, gallamine produced a dose-related potentiation of the bronchoconstriction induced by electrical stimulation of the cervical vagus nerves; (+)-tubocurarine and suxamethonium lacked this effect. 2 The bronchoconstriction produced by intravenous injection of acetylcholine or histamine, however, was not potentiated by gallamine. 3 Vagally-induced bradycardia was abolished by gallamine, confirming antagonism of the effect of acetylcholine on muscarinic receptors in the heart. 4 The muscarinic receptor agonist pilocarpine, had the opposite effect to gallamine in the lung as it inhibited vagally-mediated bronchoconstriction. 5 Pretreatment of guinea-pigs with either guanethidine or propranolol did not affect the gallamine-induced potentiation of vagally-mediated bronchoconstriction. 6 The potentiating effect of gallamine in the lung can be explained by blockade of inhibitory, muscarinic receptors located in the parasympathetic nerves supplying the lungs.

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“…Acetylcholine released in the absence of nerve stimulation (Kilbinger and Wessler, 1980b) or accumulating in the synaptic space after treatment with an AchE inhibitor (Kilbinger and Wessler, 1980a) can activate presynaptic muscarinic autoreceptors. Since basal tone was reduced by 4-DAMP (Table 1) and a low dose of neostigmine promoted smooth muscle contraction (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…2), Ach was released at the neuroeffector junction in the absence of cholinergic receptor activation. Since scopolamine alone increased Ach release from guinea pig ileum (Kilbinger and Wesler, 1980b) by blocking presynaptic muscarinic autoreceptors on enteric cholinergic neurons (Dzieniszewski and Kilbinger, 1978; Kilbinger, 1977; Kilbinger and Wesler, 1980a), it is likely that blocking presynaptic autoreceptors with low dose scopolamine enhanced endogenous Ach release resulting in activation of additional postjunctional muscarinic receptors, thereby augmenting bethanechol-induced initial contractions (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

Cellini

Jukic

LePard

2011

Autonomic Neuroscience

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Both delayed gastrointestinal transit and autonomic neuropathy have been documented in patients with diabetes mellitus. The mechanism of neostigmine, an agent that mimics release of acetylcholine from autonomic neurons by prokinetic agents, to contract smooth muscle, despite dysfunctional enteric neural pathways, was determined using isolated ilea from STZ-treated and control guinea pigs. Both bethanechol- and neostigmine-induced contractions were stronger in diabetic ileum. Bethanechol-induced contractions of control but not diabetic ileum were increased by low dose scopolamine suggesting reduced activation of presynaptic muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4-DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly, reduced neostigmine-induced contractions of control and diabetic ilea. The amount of acetylcholine, inferred from tissue choline content, was increased in diabetic ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors contributed more strongly to neostigmine-induced contractions in diabetic than control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated from sodium nitroprusside was comparable to control ileum, but smooth muscle relaxation by L-arginine using neuronal nitric oxide synthase to generate nitric oxide was weaker in diabetic ileum with evidence for a role for inducible nitric oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted ileum from diabetic animals but by a different mechanism including stronger activation of postjunctional muscarinic receptors, greater synaptic acetylcholine, stronger activation of noncholinergic excitatory pathways, and weaker activation of inhibitory pathways. A selective medication targeting a specific neural pathway may more effectively treat disordered gastrointestinal transit in patients with diabetes mellitus.

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Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum

Cited by 52 publications

References 19 publications

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

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

Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

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Pre- and postsynaptic effects of muscarinic agonists in the guinea-pig ileum

Cited by 52 publications

References 19 publications

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

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

Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea‐pig

Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated ileum from STZ diabetic guinea pigs

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

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