Role of recombinant human glicentin in the normal human jejunum: an in vitro study

Abstract

Background/aims: Glicentin (GL) is known as an inhibitory factor for alimentary tract movement and the possibility that GL may be a neuromodulator of the non-adrenergic non-cholinergic (NANC) inhibitory nerves has been reported from animal experiments. Since sufficient amounts of GL have not been available for the physiological studies, there is no report concerning the effects of GL on the enteric nervous system in the normal human small intestine. Recently synthesized recombinant human GL (rh-GL) has become available to study the physiological action of GL. To clarify the physiological significance of GL in the normal human small intestine, enteric nervous responses to GL in the normal small bowel were investigated.

Methodology: Normal jejunal muscle strips (thirty-two preparations) derived from patients who underwent jejunal resection for advanced gastric cancers (14 cases) were used. The subjects consisted of 10 men and 4 women, aged from 48 to 66 years with a mean age of 59.9 years. A mechanographic technique was used to evaluate the in vitro jejunal muscle responses to GL (recombinant human GL; rh-GL) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. All muscle strips used in this study reacted to the electrical field stimulation (EFS), which was thus suitable for stimulation of enteric nervous system.

Results: In experiment I (the responses to rh-GL after blockade of the adrenergic and cholinergic nerves) the inhibition reaction ofjejunal contraction movement was concentration-dependent; 0% at 1 x 10(-9) g/mL, 6.3% at 1 x 10(-8) g/mL, 12.5% at 1 x 10(-7) g/mL, and 43.8% at 1 x 10(-6) g/mL. The remaining muscle strips demonstrated no reaction to rh-GL. In addition, significant differences were noted between 1 x 10(-9) and 1 x 10(-6) g/mL, between 1 x 10(-8) and 1 x 10(-6) g/mL, and between 1 x 10(-7) and 1 x 10(-6) g/mL (P=0.0005, P=0.0066, P=0.0359, respectively). Rh-GL concentration-dependently inhibited a contraction reaction after blockade of the adrenergic and cholinergic nerves. In experiment II (responses to rh-GL following administration of tetrodotoxin) tetrodotoxin did not block the inhibition of contraction reaction in response to rh-GL in the human jejunum. Inhibition reaction of contraction movement was seen in the jejunal muscle strips, as in experiment I.

Conclusions: GL plays an important role in the regulating inhibition of the contraction reaction in normal human jejunum via NANC nerves, and has a direct action on the jejunal muscle receptor.