Aim: In this study we investigated the effects of ligands of opioid receptors of d-type mainly - hexapeptides Tyr-D-Ala-Gly-Phe-Leu-Arg and Tyr-D-Ala-Gly-Phe-Leu-Glu on gastric secretion stimulated by activation of neurons in dorsal nucleus of the vagus. Increased activity of the named neurons in the medulla oblongata was obtained by the infusion of selective blocker of carbohydrate metabolism 2-deoxy-D-arabinohexose ("Fluka") at the dose of 50 mg/kg i.v.
Methods: The experiments were performed on 3 dogs with gastric fistula according to "The Guiding Principles in the Care and Use of Animals" of American Physiological Association. Peptides were infused intravenously at the dose of 50 mg/kg/h. Naloxone hydrochloride ("Sigma") at the dose of 0.1 mg/kg i.v. has been used as opioid receptors antagonist.
Results: The highest level of stimulating effect of glucose isomer was recorded from the 30th till the 60th minute of the experiment. Gastric juice secretion increased 13.6 times, acid release in its content was 80 times more than in the basal level, pepsin release - 17.4 times. Infusion of enkephalin-analog D-Ala2-Arg6 reliably (p<0.001) reduced the volume of gastric juice secretion and significantly changed the secretion character. Pepsin release at this period was 17.6±7.0% of the control level. Protein release in its content reduced reliably (p<0.05), as well as acid release (p<0.01). Activation of opioid receptors by hexapeptide analog D-Ala2-Glu6 caused the strong inhibition of gastric secretion in all analysed positions. Effects of this peptide were stronger than that of enkephalin analog D-Ala2-Arg6. Naloxone infusion almost completely prevented enkephalin-induced inhibition of gastric secretion excited by vagal stimulation. Probable mechanism of the described effects of opioid receptors activation is the change of functional state of the neurons that control the functioning of gastric glandulocytes. These neurons can be located both in the central nervous system, and in the enteral nervous system. The observed peptides in the doses we have used do not penetrate over hemato-encephalic barrier.
Summary: Consequently, vagolytic effects that we have found are probably related to activation of opioid receptors of neurons of the enteral nervous system. That proves that enkephalinergic influence on the enteral cholinergic structures, that form tonic effect on the function of gastric glandulocytes, is implemented through the modulation of the functional state of the neurons of the enteral nervous system.