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Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (Ovis aries)

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Abstract

The effects of intravenous infusion of proglumide on regular ruminal contractions were examined in conscious sheep using doses that inhibit pancreatic exocrine secretion. After a control period of 20 min, proglumide was infused intravenously for 40 min at a dose of 15, 30 or 60 μmol/kg per min and venous blood was collected. The intravenous infusion of proglumide significantly increased the frequency of ruminal contractions at 15 μmol/kg per min without altering the amplitude, while it significantly decreased the frequency and amplitude of ruminal contractions at 30 and 60 μmol/kg per min in a dose-dependent manner. Proglumide did not increase contractile activity of the omasum, abomasum and duodenum or the plasma concentration of immunoreactive cholecystokinin (CCK). Application of proglumide at 1–30 mmol/L inhibited bethanechol-induced contraction in both longitudinal and circular muscle strips of the dorsal sac of the rumen. These results suggest that proglumide at a low dose acts indirectly on the rumen as a CCK receptor antagonist to increase the frequency of contractions, whereas at higher doses it inhibits cholinergic-induced contraction of the ruminal muscles or acts as an agonist to inhibit contractions in sheep. Hence, proglumide at high doses seems unsuitable for research or therapeutic use as a CCK receptor blockade in sheep.

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Abbreviations

BCh:

bethanechol

CCK:

cholecystokinin

i.c.v.:

intracerebroventricular

i.v.:

intravenous

References

  • Bueno, L., Honde, C. and Fioramonti, J., 1984. Proglumide: selective antagonism of the rumination but not gastric motor effects induced by pentagastrin in sheep. Life Sciences, 34, 475–481

    Article  PubMed  CAS  Google Scholar 

  • Cottrell, D.F. and Iggo, A., 1984. The responses of duodenal tension receptors in sheep to pentagastrin, cholecystokinin and some other drugs. Journal of Physiology (London), 354, 477–495

    CAS  Google Scholar 

  • Dethloff, L.A. and Igresia, F.A.D.L., 1992. Cholecystokinin antagonists—a toxicologic perspective. Drug Metabolism Reviews, 24, 267–293

    PubMed  CAS  Google Scholar 

  • Farningham, D.A., Mercer, J.G. and Lawrence, C.B., 1993. Satiety signals in sheep: involvement of CCK, propionate, and vagal CCK binding sites. Physiology and Behavior, 54, 437–442

    Article  PubMed  CAS  Google Scholar 

  • Forster, E.R., Green, T., Elliot, M., Bremner, A. and Dockray, G.J., 1990. Gastric emptying in rats: role of afferent neurons and cholecystokinin. American Journal of Physiology, 258, G552–G556

    PubMed  CAS  Google Scholar 

  • Gardner, J.D. and Jensen, R.T., 1984. Cholecystokinin receptor antagonists. American Journal of Physiology, 246, G471–476

    PubMed  CAS  Google Scholar 

  • Gregory, P.C., 1982. Forestomach motility in the chronically vagotomized sheep. Journal of Physiology (London), 328, 431–447

    CAS  Google Scholar 

  • Hahne, W.F., Jensen, R.T. and Gardner, J.D., 1981. Proglumide and benzotript: members of a different class of cholecystokinin receptor antagonist. Proceedings of the National Academy of Sciences of the USA, 78, 6304–6308

    Article  PubMed  CAS  Google Scholar 

  • Jansen, J.B.M.J., de Jong, A.J.L. and Lamers, C.B.H.M., 1989. The cholecystokinin receptor antagonist CR1409 increases plasma cholecystokinin in rats. Regulatory Peptides, 24, 209–213

    Article  PubMed  CAS  Google Scholar 

  • Kato, S., Adachi, N., Ando, T., Mineo, H. and Ushijima, J., 1986. The effect of intravenous infusion of atropine on pancreatic exocrine secretion in sheep. Japanese Journal of Zootechnical Sciences, 56, 905–910

    Google Scholar 

  • Kermani, R.Z. and Rezaiee, A., 1993. The effects of intravenous cholecystokinin, secretin and pentagastrin on electromyographic activity of the rumen in sheep. Regulatory Peptides, 45, 371–377

    Article  PubMed  CAS  Google Scholar 

  • Le Drean, G., Le Huerou-Luron, I., Gestin, M., Desbois, C., Rome, V., Bernard, C., Dufresne, M., Moroder, L., Gully, D., Chayvialle, J.A., Fourmy, D. and Guilloteau, P., 1999. Exogenous CCK and gastrin stimulate pancreatic exocrine secretion via CCK-A but also via CCK-B/gastrin receptors in the calf. Pflügers Archives, 438, 86–93

    Article  Google Scholar 

  • Liddle, R.A., 1995. Regulation of cholecystokinin secretion by intraluminal releasing factors. American Journal of Physiology, 269, G319–327

    PubMed  CAS  Google Scholar 

  • Loewe, C.J., Grider, J.R., Gardiner, J. and Vlahcevic, Z.R., 1985. Selective inhibition of pentagastrin- and cholecystokinin-stimulated exocrine secretion by proglumide. Gastroenterology, 89, 746–751

    PubMed  CAS  Google Scholar 

  • McLeay, L.M. and Wong, M.H., 1989. Excitatory and inhibitory effects of gastrin peptides on gastric motility in sheep. American Journal of Physiology, 257, R388–R395

    PubMed  CAS  Google Scholar 

  • Mineo, H., Iwaki, N., Kogishi, K., Zabielski, R., Onaga, T. and Kato, S., 1995. Effects of intravenous infusions of cholecystokinin (CCK)-8 on exocrine and endocrine pancreatic secretion in conscious sheep. Comparative Biochemistry and Physiology A, 111, 133–138

    Article  CAS  Google Scholar 

  • Mineo, H., Iwaki, N., Kogishi, K., Onaga, T., Kato, S. and Zabielski, R., 1997. Effects of proglumide on cholecystokinin-8-induced exocrine and endocrine pancreatic responses in conscious sheep. Comparative Biochemistry and Physiology A, 118, 759–764

    Article  CAS  Google Scholar 

  • Niederau, C., Niederau, M., Williams, J.A. and Grendell, J.H., 1986. New proglumide-analogue CCK receptor antagonists: very potent and selective for peripheral tissues. American Journal of Physiology, 250, G856–G860

    PubMed  CAS  Google Scholar 

  • Noble, F. and Roques, B.P., 1999. CCK-B receptor: chemistry, molecular biology, biochemistry and pharmacology. Progress in Neurobiology, 58, 349–379

    Article  PubMed  CAS  Google Scholar 

  • Onaga, T., Hara, I., Kagawa, K., Mineo, H. and Kato, S., 1994. Cholecystokinin induces tonic contraction of omasum in sheep (abstract). Proceedings of the Society of Nutrition and Physiology, 5, 52

    Google Scholar 

  • Onaga, T., Onodera, T., Mineo, H. and Kato, S., 1995. Cholecystokinin does not act on the efferent pathway of cholinergic and adrenergic nerves to inhibit ruminal contractions in sheep (Ovis aries). Comparative Biochemistry and Physiology A, 111, 51–58

    Article  CAS  Google Scholar 

  • Onaga, T., Mineo, H. and Kato, S., 1997. Effect of L364718 on interdigestive pancreatic exocrine secretion and gastroduodenal motility in conscious sheep. Regulatory Peptides, 68, 139–146

    Article  PubMed  CAS  Google Scholar 

  • Raybould, H.E., Roberts, M.E. and Dockray, G.J., 1987. Reflex decreases in intragastric pressure in response to cholecystokinin in rats. American Journal of Physiology, 253, G165–G170

    PubMed  CAS  Google Scholar 

  • Ruckebusch, Y., 1983. Pharmacology of reticulo-ruminal motor functions. Journal of Veterinary Pharmacology and Therapeutics, 6, 245–272

    PubMed  CAS  Google Scholar 

  • Ruckebusch, Y., 1989. Gastrointestinal motor functions in ruminants. In: S.G. Schultz, J.D. Wood and B.B. Rauner (eds), The Handbook of Physiology, Section 6: The gastrointestinal system, (Oxford University Press, New York), 1225–1282

    Google Scholar 

  • Saito, A., Goldfine, I.D. and Williams, J.A., 1981. Characterization of receptors for cholecystokinin and related peptides in mouse cerebral cortex. Journal of Neurochemistry, 37, 483–490.

    Article  PubMed  CAS  Google Scholar 

  • Sakatani, N., Inui, A. and Baba, S., 1989. [The effect of cholecystokinin antagonists on satiety induced by cholecystokinin octapeptide in dogs]. Nippon Naibunpi Gakkai Zasshi, 65, 1149–1158.

    PubMed  CAS  Google Scholar 

  • Steigerwalt, R.W., Goldfine, I.D. and Williams, J.A., 1984. Characterization of cholecystokinin receptors on bovine gallbladder membranes. American Journal of Physiology, 247, G709–714

    PubMed  CAS  Google Scholar 

  • Tachibana, S., Onaga, T., Mineo, H. and Kato, S., 1995. Role of endogenous CCK in regulation of interdigestive pancreatic exocrine secretion in sheep. Comparative Biochemistry and Physiology A, 112, 103–109

    Article  CAS  Google Scholar 

  • Titchen, D.A., 1984. Gastrointestinal peptide hormone distribution, release, and action in ruminants. In: L.P. Milligan, W.L. Grovum and A. Dobson (eds.), Control of Digestion and Metabolism in Ruminants, (Prentice-Hall, Englewood Cliffs, NJ), 227–248

    Google Scholar 

  • Wettstein, J.G., Bueno, L. and Junien, J.L., 1994. CCK antagonists: pharmacology and therapeutic interest. Pharmacology and Therapeutics, 62, 267–282

    Article  PubMed  CAS  Google Scholar 

  • Williams, J.A., Bailey, A. and Steigerwalt, R.W., 1983. Effects of proglumide on pancreatic acinar cell function. Digestion, 27, 227–233

    Article  PubMed  CAS  Google Scholar 

  • Wilson, R.C., Goetsch, D.D. and Huber, T.L., 1976. Studies of mechanisms of action of secretin and pancreozymin on ruminal motility. American Journal of Veterinary Research, 37, 1131–1134

    PubMed  CAS  Google Scholar 

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Onaga, T. Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (Ovis aries). Vet Res Commun 31, 1021–1036 (2007). https://doi.org/10.1007/s11259-006-0164-z

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