Motor-modifying properties of 5-HT3 and 5-HT4 receptor agonists on ovine abomasum.

Abstract

The effects and sites of action of 5-HT3 and 5-HT4 receptor agonists and antagonists on the abomasal myoelectric activity were examined in conscious sheep, chronically fitted with intravenous (i.v.) and intracerebroventricular (ICV) cannulas and intraparietal electrodes on the gastric body and antrum. The 5-HT3 receptor agonist 2-methylserotonin, injected either i.v. (150 micrograms/kg) or ICV (5 micrograms/kg), induced an inhibition of the spiking activity in both the gastric body and antrum. This inhibition was abolished when the 5-HT3 antagonist granisetron was preinjected either i.v. (150 micrograms/kg) or ICV (15 micrograms/kg). The i.v. injection of 5-HT4 agonist 5-methoxytryptamine (200 micrograms/kg) initially provoked stimulation and thereafter inhibition of abomasal activity, while its ICV administration (10 micrograms/kg) resulted in only inhibition of the gastric body activity. BIMU 1, another 5-HT4 agonistic substance, injected i.v. (300-1000 micrograms/kg), mimicked only the stimulatory actions of 5-methoxytryptamine, while its ICV administration (10-50 micrograms/kg) had no effect on the abomasal activity. The i.v. (2000 micrograms/kg), but not the ICV (100 micrograms/kg), pre-injection of the 5-HT4 antagonist DAU 6285 blocked the stimulation of the abomasal spiking activity resulting from the i.v. injection of either 5-methoxytryptamine or BIMU 1. These results suggest that, in sheep, inhibitory 5-HT3 and excitatory 5-HT4 receptors, located at brain and peripheral levels respectively, participate in the control of the abomasal contractions.