Proglumide: selective antagonism of the rumination but not gastric motor effects induced by pentagastrin in sheep.

The effect of intravenous (IV) vs intracerebroventricular (ICV) administrations of pentagastrin on gastro-intestinal motility and rumination were investigated by electromyography in sheep; these effects were compared to those obtained after a previous IV or ICV injection of proglumide. When ICV administered at a dose of 20 ng X kg-1, pentagastrin did not significantly affect the frequency of reticular and abomasal spiking activity but elicited a 13 to 37 min period of rumination after a delay of 23 +/- 7 min. In contrast, when IV infused at a rate of 20 ng X kg-1 X h-1 during 20 min, pentagastrin inhibited significantly the frequency of reticular and abomasal contractions for 30 to 40 min but did not induce rumination. Proglumide ICV administered (0.8 mg X kg-1) abolished the rumination induced by central injection of pentagastrin whereas a 10 times higher dose administered systemically (8 mg X kg-1 IV) did not block these effects. Both of ICV and IV administrations of proglumide at respectively 0.8 and 8 mg X kg-1 were unable to antagonize the inhibitory effects of pentagastrin on reticulum and abomasum motility. It was concluded that (i) pentagastrin acts centrally to induce rumination and that (ii) proglumide selectively blocks these effects but not the pentagastrin induced gastro-intestinal hypomotility.