MOTOR-MODIFYING PROPERTIES OF 5-HT(3) AND 5-HT(4) RECEPTOR AGONISTS ON OVINE ABOMASUM

The effects and sites of action of 5-HT3 and 5-HT, receptor agonists and antagonists on the abomasal myoelectric activity were examined in conscious sheep, chronically fitted with intravenous (IV) and intracerebroventricular (ICV) cannulas and intraparietal electrodes on the gastric body and antrum. The 5-HT3 receptor agonist 2-methylserotonin, injected either IV (150 mug/kg) or ICV (5 mug/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 IV (150 mug/kg) or ICV (15 mug/kg). The IV injection of 5-HT4 agonist 5-methoxytryptamine (200 mug/kg) initially provoked stimulation and thereafter inhibition of abomasal activity, while its ICV administration (10 mug/kg) resulted in only inhibition of the gastric body activity. BIMU 1, another 5-HT4 agonistic substance, injected IV (300-1000 mug/kg), mimicked only the stimulatory actions of 5-methoxytryptamine, while its ICV administration (10-50 mug/kg) had no effect on the abomasal activity. The IV (2000 mug/kg), but not the ICV (100 mug/kg), pre-injection of the 5-HT4 antagonist DAU 6285 blocked the stimulation of the abomasal spiking activity resulting from the IV 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.