Masaki Maeda-Hagiwara

Intracerebroventricular Pressure Inhibits Gastric Antral and Duodenal Contractility but Not Acid Secretion in Conscious Rabbits

Acute nausea characteristically accompanies head injury or increased intracranial pressure, or both. The etiology of this symptom is unclear. We studied the effect of increased intracranial pressure on gastric antral and duodenal contractility and gastric acid secretion in conscious rabbits. Intracerebroventricular pressure was maintained at 3, 8, or 13 cmH2O using normal saline perfused into the lateral cerebral ventricle and gastric antral and duodenal contractility was monitored using chronically implanted strain gauge force transducers. Gastric acid secretion was measured in a separate group of rabbits with chronically implanted gastric cannulas. Increased intracerebroventricular pressure (13 cmH2O) resulted in an immediate suppression of the amplitude of gastric and duodenal contractions by greater than 80% and greater than 60%, respectively. After normalization of intracerebroventricular pressure, the contractile pattern returned to basal levels. Intravenous bolus injection of bethanechol reversed the suppression of gastric antral contractility induced by increased intracranial pressure. Increased pressure for 2 h did not modify gastric acid output as compared with normal pressure controls, whereas atropine significantly inhibited and histamine stimulated gastric acid secretion in the same animals maintained at normal pressure. These results demonstrate that acutely increased intracranial pressure rapidly and reversibly inhibits gastric and duodenal motor function in conscious rabbits.

Enhancement by intracerebroventricular thyrotropin‐releasing hormone of indomethacin‐induced gastric lesions in the rat

1 Effects of the intracerebroventricular thyrotropin‐releasing hormone (TRH) on gastric mucosa were studied in rats. 2 TRH (3 and 10 μg rat−1 i.c.v.) produced slight gastric lesions and also aggravated indomethacin‐, aspirin‐ or 5‐hydroxytryptamine (5‐HT)‐induced gastric lesions, while restraint and cold stress‐induced lesions were not influenced by TRH. 3 Bethanechol used at a dose sufficient to produce acid secretion did not influence the gastric mucosa in intact or indomethacin‐treated rats. 4 Enhancement of indomethacin‐induced gastric lesions by TRH was not inhibited to any significant degree by atropine 0.1 mg kg−1 s.c., which prevented TRH‐induced gastric acid secretion, but tended to be inhibited by phentolamine, 2.5 mg kg−1 i.p. 5 It is concluded that the enhancement by TRH of indomethacin‐induced gastric lesions is due to a combination of the central and peripheral actions of the ulcerogenic agents.

Central nervous system action of TRH to stimulate gastric function and ulceration

Intracisternal or intracerebroventricular injection of TRH (0.1-10 micrograms) in rats stimulated the secretion of gastric acid and pepsin secretion, increased gastric mucosal blood flow and gastric contractility and emptying, induced gastric hemorrhagic lesions and aggravated experimental ulcers elicited by aspirin, serotonin or indomethacin. TRH action was dose-dependent, rapid in onset and central nervous system-mediated by activation of the parasympathetic outflow to the stomach and cholinergic receptors. The stable TRH analog, RX 77368, was more potent and longer lasting than TRH. TRH and its stable analog appear as new chemical probes to produce centrally-mediated vagal-dependent stimulation of gastric function and experimental ulcers. The physiologic role of endogenous TRH in the central regulation of gastric function and ulceration remains to be established.

Intracerebroventricular injection of a TRH analogue, γ-butyrolactone-γ-carbonyl-L-histidyl-prolinamide, induces gastric lesions and gastric acid stimulation in rats

SummaryThe effects of TRH and its biologically stable analogue, γ-butyrolactone-γ-carbonyl-l-histidyl-l-prolinamide (DN-1417), on gastric mucosa and acid secretion were examined in rats. Intracerebroventricular (ICV) injection of DN-1417 (0.1–10 μg) caused a dose-dependent gastric lesion in the corpus and antrum 6 h after administration. The gastric lesions produced by 1 μg of DN-1417 were more severe than those produced by ICV TRH (10 μg), intravenous DN-1417 (200 μg) and stress. Although the lesion-generating effect of TRH (10 μg) tended to be reduced 6 h after the injection, that of DN-1417 (1 μg) was sustained during 6 h. Atropine (0.1 and 1 mg/kg s.c.) inhibited DN-1417-induced gastric lesions in a dose-related manner while sulpiride (10 and 30 mg/kg s.c.), haloperidol (1 mg/kg i.p.), phentolamine (1 and 5 mg/kg s.c.) and yohimbine (5 mg/kg s.c.) did not prevent the lesions. ICV DN-1417 also stimulated basal gastric acid secretion and the effect was stronger and longer-lasting than that of TRH. Atropine (0.1 mg/kg s.c.) stopped DN-1417-stimulated gastric acid secretion. In conclusion, the possibility that TRH may be involved in the CNS modulation of gastric mucosal integrity deserves further attention. The enhanced potency of action of DN-1417 over TRH could make ICV injection of this peptide a useful tool for inducing centrally-mediated gastric lesions in rats.

Influence of Clonidine and a New Related Imidazoline Derivative (Tizanidine) on Rat Gastric Mucosa

The effects of a novel imidazoline derivative (tizanidine) on experimental ulcers and glycoproteins in the gastric mucosa and juice of rats were examined and compared with that of clonidine. Tizanidine and clonidine inhibited indomethacin ulcer and aspirin ulcers. Tizanidine, however, did not influence stress ulcer while clonidine showed an inhibitory effect. Although tizanidine and clonidine did not increase glycoproteins in the gastric mucosa, they prevented aspirin-induced changes of glycoproteins in the gastric mucosa and juice, as well as aspirin-induced gastric ulcers. The results suggest that, as with clonidine, tizanidine inhibits drug-induced gastric ulcers and that tizanidine-mediated gastric mucosal protection may prevent gastric ulcers induced by anti-inflammatory agents.

Bromocriptine inhibits 2-deoxy-d-glucose-stimulated gastric acid secretion in the rat

The influence of bromocriptine on the secretagogue-induced gastric acid secretion was examined in rats. The drug inhibited the gastric acid secretion centrally stimulated by 2-deoxy-D-glucose (2DG) in anesthetized or conscious rats. Apomorphine also prevented 2DG-induced acid secretion in anesthetized rats but not in conscious rats. Neither bromocriptine nor apomorphine significantly influenced the acid secretion induced peripherally by electrical vagus stimulation or gastrin. The antisecretory effect of bromocriptine was reversed by dopamine antagonists in anesthetized or conscious rats, but not by apomorphine in anesthetized rats. The results suggest that in rats, the antisecretory effect of bromocriptine on 2DG-stimulated acid secretion is partly due to its central dopamine agonistic action, but that of apomorphine may be due to dopaminergic plus other mechanisms.