Nicotine applied into the dorsal motor nucleus of the vagus inhibits enhanced gastric acid output and mucosal blood flow in rats

doi:10.1016/0014-2999(86)90251-7

European Journal of Pharmacology

Volume 121, Issue 3, 4 March 1986, Pages 313-318

https://doi.org/10.1016/0014-2999(86)90251-7 Get rights and content

Abstract

The effects of nicotine microinjected into several brain regions on the centrally elevated gastric acid output and mucosal blood flow (MBF) were examined in anesthetized rats. Intravenous administration of 2-deoxy-D-glucose (2-DG) induced increases in gastric acid output and MBF. These increases were inhibited dose dependently by nicotine microinjected into the dorsal motor nucleus of the vagus (NDV) but not into various hypothalamic regions. This effect of nicotine was abolished with concomitantly administered hexamethonium and was not observed in reserpine-pretreated animals. Electrical stimulation of the lateral hypothalamic area (LHA) induced an increase in gastric acid output. This increase was completely inhibited when nicotine was microinjected into the NDV 5 min before stimulation. This inhibitory effect of nicotine was abolished by concomitantly administered hexamethonium and by intraventricular pretreatment with phentolamine, but not with propranolol. These results suggest that activation of nicotinic receptors within the NDV releases noradrenaline and that there is a resultant inhibition of gastric acid output and MBF.

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Citation Excerpt :
Electrolytic lesions of the DMV reduce GMBF, with the greatest inhibitory effects coming from the caudal most lesions versus lesions placed rostrally in the DMV (Chan et al., 1995). Microinjection of nicotine into the DMV attenuates increases in GMBF (and gastric acid secretion) that occurs with intravenous administration of 2-deoxy-d-glucose (Nagata et al., 1986). Microinjection of thyrotropin releasing hormone (TRH) into the DMV and NTS induced a dose dependent increase in GMBF and gastric acid secretion (Okuma et al., 1987; Tache et al., 1989).
The theory of gastric CO₂ ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO₂ during respiratory acidosis. Neurons in the cSC, which is a site of CO₂ chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO₂ from blood. CO₂ is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO₂ in the stomach lumen from the reaction between H⁺ and HCO₃⁻. Respiratory acidosis and gastric CO₂ distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO₂ upwards by bulk flow along an abdominal-to-esophageal (= intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO₂ is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO₂ ventilation provides explanations for (1) the postprandial increase in expired CO₂ and (2) the negative $P {(blood - expired)}_{C O_{2}}$ difference that occurs with increased inspired CO₂. Furthermore, it is postulated that gastric CO₂ ventilation and alveolar CO₂ ventilation are coordinated under dual control by CO₂ chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO₂ chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO₂ elimination. A distributed CO₂ chemosensitive network—at least nine different areas in the CNS, including the cSC, have been reported to date—may reflect the complexity and dynamic nature of the fundamental neural circuitry required to achieve CO₂/pH regulation across multiple organ systems under various states of arousal, oxygenation, pH status, and redox state. Moreover, coordination of respiratory and digestive control networks through the cSC could also account for the frequent co-expression of pulmonary diseases that cause chronic respiratory acidosis (and overstimulation of cSC neurons) with peptic ulcer disease or gastroesophageal reflux disease.
Effects of smoking and nicotine on the gastric mucosa: A review of clinical and experimental evidence
1994, Gastroenterology
Epidemiological and experimental evidence have shown that nicotine has harmful effects on the gastric mucosa. The mechanisms by which cigarette smoking or nicotine adversely affect the gastric mucosa have not been fully elucidated. In this report, clinical and experimental data are reviewed. The effects of nicotine from smoking on gastric aggressive or defensive factors are discussed. Nicotine potentiates gastric aggressive factors and attenuates defensive factors; it also increases acid and pepsin secretions, gastric motility, duodenogastric reflux of bile salts, the risk of Helicobacter pylori infection, levels of free radicals, and platelet-activating factor, endothelin generation, and vasopressin secretion. Additionally, nicotine impairs the therapeutic effect of H₂-receptor antagonists and decreases prostaglandin synthesis, gastric mucosal blood flow, mucus secretion, and epidermal growth factor secretion. Although many of the studies provide conflicting results, the bulk of the evidence supports the hypothesis that nicotine is harmful to the gastric mucosa.
Localization of the stomach-projecting neurons in the dorsal motor nucleus of the vagus nerve in the guinea pig
1993, Journal of the Autonomic Nervous System
The medullary origin of cells of the cervical vagus nerve and the vagal innervation of the stomach in the guinea pig were studied using the retrograde transport of horseradish peroxidase. The horseradish peroxidase was injected into the cervical portion of the vagus nerve, and also into the greater or lesser curvature of the stomach. The animals were perfused with fixative two days after the injection. The medulla oblongata containing the dorsal motor nucleus of the vagus nerve was sectioned and processed histochemically with the tetramethyl benzidine method. The injection of horseradish peroxidase in the cervical vagus nerve resulted in heavy retrograde labelling of neurons in the ipsilateral dorsal motor nucleus and in the nucleus ambiguus. Following the injection of horseradish peroxidase into the greater curvature of the stomach, the stomach-projecting neurons which were bilaterally labelled were localized in the dorsal and dorsolateral part of the dorsal motor nucleus. Although also bilaterally labelled in the dorsal and dorsolateral part of the dorsal motor nucleus, the neurons projecting to the lesser curvature of the stomach were predominantly (approx. 70%) located in the left dorsal motor nucleus. Our study suggests that the parasympathetic preganglionic neurons innervating the greater and lesser curvatures of the stomach are organized viscerotopically in the dorsal motor nucleus in the guinea pig.
Vagal motor neurons innervating the stomach are site-specifically organized in the dorsal motor nucleus of the vagus nerve in rats
1990, Journal of the Autonomic Nervous System
The aim of the present study was to examine the neuroanatomical relationship between the brainstem and the stomach. For this purpose, by means of a horseradish peroxidase retrograde method, we identified the distribution of individual parasympathetic preganglionic neurons projecting to three specific gastric regions that have structural and functional differences in the rat stomach. Preganglionic neurons innervating the ventral forestomach were mainly distributed in the lateral part of the left dorsal motor nucleus of the vagus nerve, while those innervating both ventral corpus and antrum were chiefly located in the medial part of the left dorsal motor nucleus. On the other hand, preganglionic neurons projecting to the dorsal forestomach and the dorsal corpus and antrum were predominantly observed in the lateral and the medial part of the right dorsal motor nucleus, respectively. These results suggest that parasympathetic preganglionic neurons innervating the stomach are site-specifically organized in the dorsal motor nuclei.
Dual effect of nicotine injected in the cerebral ventricles on rat gastric motility
1989, European Journal of Pharmacology
Intracerebroventricularly (i.c.v.) administered nicotine 50 and 100 nmol produced dual changes, an early decrease and a succesive increase in gastric motility in urethane-anesthetized rats in which an intragastric balloon had been placed. These dual effects of nicotine were significantly antagonized by simultaneously administered hexamethonium i.c.v. but not by splanchnicectomy or by pretreatment with reserpine. Both atropine pretreatment and vagotomy abolished the stimulating effect of nicotine on gastric motility. Nicotine administered i.c.v. to bilaterally vagotomized rats did not affect gastric motility which was however enhanced by electrical stimulation of the vagus nerve. These observations suggest that central activation of the vagal cholinergic component results in excitation and central activation of the vagal non-adrenergic inhibitory component with i.c.v. administered nicotine results in inhibition of gastric motility. Sympathoadrenal systems and central monoaminergic mechanisms are probably not involved in the inhibitory effect of i.c.v. administered nicotine on gastric motility.
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1989, Drug and Alcohol Dependence
In mice, nicotine produces dose-dependent mydriasis following interperitoneal or intracerebroventicular administration but not after local application through the conjunctival sac. Since mydriasis is not prevented by cervical sympathectomy, it is likely to be due to central inhibition of the parasympathetic tone.
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The easily measurable examination of the pupillary responses provide a convenient method for the investigation of mechanisms underlying tolerance to nicotine.

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Nicotine applied into the dorsal motor nucleus of the vagus inhibits enhanced gastric acid output and mucosal blood flow in rats

Abstract

European J. Pharmacol.

Life Sci.

European J. Pharmacol.

Life Sci.

Life Sci.

European J. Pharmacol.

European J. Pharmacol.

Neuropharmacology