Ghrelin stimulates gastric motility of the guinea pig through activation of a capsaicin-sensitive neural pathway: in vivo and in vitro functional studies


Takio Kitazawa, Department of Pharmacology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
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Background  Ghrelin stimulates gastric motility in rats, mice and humans. Although ghrelin and the ghrelin receptor are known to be expressed in the guinea-pig gastrointestinal tract, the effects of ghrelin on gastric motility have not been examined. Aim of the present study was to clarify the motor-stimulating action of ghrelin in the guinea-pig stomach.

Methods  Gastric motility was measured as intraluminal pressure changes using a balloon inserted in the stomach of urethane-anaesthetized guinea pigs. The effects of ghrelin on gastric muscle contraction and [3H]-efflux from [3H]-choline-loaded strips were investigated in vitro.

Key Results  Ghrelin (0.3–30 μg kg−1, i.v.) increased gastric motility in a dose-dependent manner but des-acyl ghrelin was ineffective. The action of ghrelin was completely inhibited by hexamethonium and d-Lys3-growth-hormone releasing peptide-6. Atropine partially decreased the stimulatory action of ghrelin. In capsaicin-pretreated guinea pigs, the ghrelin-induced response was markedly decreased. Ghrelin (1 μmol L−1) did not affect [3H]-efflux in non-stimulated preparations but significantly decreased electrical field stimulation (EFS)-induced [3H]-efflux. l-Nitro arginine methylester (l-NAME) attenuated the inhibition of [3H]-efflux by ghrelin. Ghrelin did not cause any mechanical changes in gastric strips. Electrical field stimulation caused relaxation of gastric strips, which changed to atropine-sensitive contraction in the presence of l-NAME. Relaxation induced by EFS was slightly potentiated, but the EFS-induced contraction was not affected by ghrelin.

Conclusions & Inferences  Ghrelin stimulates gastric motility of the guinea pig through activation of capsaicin-sensitive vago-vagal reflex pathway including efferent cholinergic neurons. Peripheral ghrelin receptors on enteric nitrergic nerves might affect the ghrelin-induced gastric action by releasing nitric oxide.