Gastric acid secretion cholinergic

Histamine receptors were first divided into two subclasses Hi and H2 by Ash and Schild (1966) on the basis that the then known antihistamines did not inhibit histamine-induced gastric acid secretion. The justification for this subdivision was established some years later when Black (see Black et al. 1972) developed drugs, like cimetidine, that affected only the histamine stimulation of gastric acid secretion and had such a dramatic impact on the treatment of peptic ulcers. A recently developed H2 antagonist zolantidine is the first, however, to show significant brain penetration. A further H3 receptor has now been established. It is predominantly an autoreceptor on histamine nerves but is also found on the terminals of aminergic, cholinergic and peptide neurons. All three receptors are G-protein-coupled but little is known of the intracellular pathway linked to the H3 receptor and unlike Hi and H2 receptors it still remains to be cloned. Activation of Hi receptors stimulates IP3 formation while the H2 receptor is linked to activation of adenylate cyclase. 

Gl disease/dysfunction Tacrine is an inhibitor of cholinesterase and may be expected to increase gastric acid secretion caused by increased cholinergic activity. Therefore, closely monitor patients at increased risk for developing ulcers for symptoms of active or occult Gl bleeding. 

Peds. GERD 10 mg/kg PO bid in doses, 150 mg bid max T in renal impair Caution [B, +] Contra H2-Receptor antagonist sensitivity Disp Caps, sol SE Dizziness, HA, constipation, D Interactions t Effects OF salicylates, EtOH X effects W/ antacids, tomato/mixed veg juice EMS Concurrent salicylate use can t risk of salicylate tox smoking t gastric acid secretion which can aggravate Dz Sxs OD May cause cholinergic-type effects (SLUDGE) activated charcoal may be effective... 

Additional effects of nicotine include an increase in gastric acid secretion and an increase in the tone and motility of the gastrointestinal tract. These effects are produced because of the predominance of cholinergic input to these effector systems. 

Aihaara T et al Cholinergically stimulated gastric acid secretion is mediated by M3 and M5 but not Mi muscarinic acetylcholine receptors in mice. Am J Physiol 2005 288 G1199. 

H3 receptors suppress gastric acid secretion, and this is evoked by cholinergic stimuli. H3 receptors exist outside the parietal cells and seem to be located on cholinergic and nonadrenergic noncholinergic neurons of the myenteric plexus, where they inhibit the release of neurotransmitters. The agonist and antagonist for H3 receptors are alpha-methylhistamine and thioperamide, respectively. 

Propantheline, a muscarinic cholinergic receptor antagonist, competitively blocks acetylcholine s actions at cholinergic neuroeffector sites, decreasing GI motility and inhibiting gastric acid secretion. 

Anticholinergics (cholinergic blocking drug) reduce gastric motility and decrease the amount of acid secreted by the stomach (see Chap. 25). Examples of anticholinergics used for GI disorders include propantheline (Pro-Banthine) and glycopyrrolate (Robinul). 

In the mouse, whereas no evidence of H3 receptors was found in isolated gastric glands (Muller et al., 1993), in the whole stomach, (R)a-methylhistamine actually increased, and thioperamide decreased acid secretion, thus indicating a definite stimulatory role for H3 receptors in this species (Table 2). Apparently, this excitatory effect, which contrasts with the observations obtained in other models, was due to an inhibitory effect on somatostatin release from fundic D cells (Schubert et al., 1993 Vuyyuru and Schubert 1993). Also, an inhibitory effect on somatostatin secretion mediated by H3 agonists was observed in other species (rat and dog). However, contrarily to what might have been expected, in these species, the inhibitory effect on somatostatin is not followed by an increase in acid secretion, but it is instead followed by a decrease, owing to the predominant H3-mediated inhibition on the release of excitatory mediators (histamine, acetylcholine) from other sites (ECL, cholinergic nerve terminals)... 

Muller, M.J., Padol, I., Hunt, R.H., 1993. Acid secretion in isolated murine gastric glands classification of histaminergic and cholinergic receptors. Gastroenterology 104 (Suppl), A151. 

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