The role of adrenoreceptors in the implementation of the stimulatory effect of serotonin on the gastric motor activity

Purpose of the study — study of the role of adrenoreceptors in the development of the stimulatory action of serotonin on the gastric motor activity.Materials and methods. The experiments were performed on rats (27) of the Wistar line in the surgical stage of anesthesia. Electromyogram and hydrostatic pressure in the stomach cavity were recorded using a BioAmp ML132 amplifier (Adinstruments, Australia), an Maclab 8e analog-to-digital converter (Adinstruments, Australia), a Macintosh Performa 6400/180 computer, and Chart 4.2.3. program. Serotonin injected into the body to intact animals and against the background of separate and joint blockade of α- and β-adrenoreceptors.The results of the study. In experiments on rats established that the preliminary simultaneous blockade of α- and β- adrenoreceptors leads to an increase in the stimulatory effect of the stomach with the introduction of serotonin by 58%, blockade of α-adrenoreceptors only — by 62%, β-adrenoreceptor blockade — by 89%. In intact animals, the stimulatory eff ect of serotonin is only + 26%. Simultaneous blockade of α- and β-adrenoreceptors and blockade of α-adrenoreceptors only (without serotonin administration) did not aff ect the gastric motor activity of intact animals. Blockade only β-adrenoreceptors will lead to an increase in gastric contractions by 34%.Conclusion. Intact α- and β-adrenoreceptors inhibit the stimulatory eff ect of serotonin on gastric motor activity.

Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach

Inhibitory motor neurons regulate several gastric motility patterns including receptive relaxation, gastric peristaltic motor patterns, and pyloric sphincter opening. Nitric oxide (NO) and purines have been identified as likely candidates that mediate inhibitory neural responses. However, the contribution from each neurotransmitter has received little attention in the distal stomach. The aims of this study were to identify the roles played by NO and purines in inhibitory motor responses in the antrums of mice and monkeys. By using wild-type mice and mutants with genetically deleted neural nitric oxide synthase ( Nos1 −/−) and P2Y1 receptors ( P2ry1 −/−) we examined the roles of NO and purines in postjunctional inhibitory responses in the distal stomach and compared these responses to those in primate stomach. Activation of inhibitory motor nerves using electrical field stimulation (EFS) produced frequency-dependent inhibitory junction potentials (IJPs) that produced muscle relaxations in both species. Stimulation of inhibitory nerves during slow waves terminated pacemaker events and associated contractions. In Nos1 −/− mice IJPs and relaxations persisted whereas in P2ry1 −/− mice IJPs were absent but relaxations persisted. In the gastric antrum of the non-human primate model Macaca fascicularis, similar NO and purine neural components contributed to inhibition of gastric motor activity. These data support a role of convergent inhibitory neural responses in the regulation of gastric motor activity across diverse species.

Roles of prostaglandin E2-EP1 receptor signaling in regulation of gastric motor activity and emptying

It is widely accepted that the inhibition of gastric motor activity as well as the maintenance of gastric mucosal blood flow and mucous secretion are important for the homeostasis of the gastric mucosa. The present study was performed to ascertain whether or not endogenous PGs, which can protect the stomach from noxious stimuli, affect gastric motor activity and emptying. The myoelectrical activity of rat gastric smooth muscle was increased at intragastric pressures of over 2 cmH2O. Replacement of intragastric physiological saline with 1 M NaCl solution significantly increased PGI2 and PGE2 in stomach and suppressed the myoelectrical activity under a pressure of 2 cmH2O by 70%. Indomethacin inhibited the suppression of myoelectrical activity by 1 M NaCl. The myoelectrical activity under a pressure of 2 cmH2O was suppressed by continuous infusion of a selective EP1 agonist (ONO-DI-004, 3–100 nmol·kg−1·min−1) into the gastric artery in a dose-dependent manner, but not by that of the PGI receptor agonist beraprost sodium (100 nmol·kg−1·min−1). Suppression of myoelectrical activity with 1 M NaCl was inhibited by continuous infusion of a selective EP1 antagonist (ONO-8711, 100 nmol·kg−1·min−1) into the gastric artery. Furthermore, gastric emptying was tested in EP1 knockout mice and their wild-type counterparts. Gastric emptying was strongly suppressed with intragastric 1 M NaCl in wild-type mice, but this 1 M NaCl-induced suppression was not seen in EP1 knockout mice. These results suggest that PGE2-EP1 signaling has crucial roles in suppression of myoelectrical activity of gastric smooth muscles and inhibition of gastric emptying and that EP1 is an obvious target for drugs that control gastric emptying.