Summary
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1.
A peristaltic reflex preparation of the isolated guinea-pig ileum was developed which had an intact vascular supply and into which drugs were infused intraarterially. Intraluminal pressure and intraluminal volume propelled per time were recorded. Peristalsis was triggered by raising the intraluminal pressure at constant time intervals.
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2.
Caerulein (>0.2 pmoles min−1), substance P (>5 pmoles min−1), 5-hydroxytryptamine (>90 pmoles min−1), and bethanechol (>900 pmoles min−1) initiated peristalsis when intraluminal pressure was not raised.
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3.
Under conditions of isotonic longitudinal contraction pressure-induced peristalsis was reduced by substance P and bethanechol, but not affected by caerulein and 5-hydroxytryptamine.
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4.
Under conditions of isometric longitudinal contraction, caerulein (0.5 pmoles min−1), substance P (2.4 pmoles min−1), 5-hydroxytryptamine (180 pmoles min−1), and bethanechol (355 pmoles min−1) increased the efficiency of the peristaltic reflex.
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5.
d-Ala2-d-met5-enkephalin (>27 pmoles min−1) and d-ala2-mephe4-met-(O)5-ol-enkephalin (FK 33-824, >11 pmoles min−1) inhibited the peristaltic reflex, thus exceeding the potency of morphine, atropine, noradrenaline, hexamethonium, and isoprenaline 100–1000-fold.
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6.
ATP, 13-nle-motilin, somatostatin, and vasoactive intestinal polypeptide had no influence on the peristaltic reflex.
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7.
Since substance P and enkephalin are the most potent compounds of mammalian origin in affecting peristalsis it is concluded that they are involved in the nervous mechanisms of the peristaltic reflex.
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References
Beleslin, D. B., Varagić, V.: The effect of substance P on the peristaltic reflex of the isolated guinea-pig ileum. Br. J. Pharmacol. 13, 321–325 (1958)
Beleslin, D. B., Varagić, V.: The effect of substance P on the peristaltic reflex when acting on the outside of the isolated guinea-pig ileum. J. Pharm. Pharmacol. 11, 99–103 (1959)
Bennett, A.: Relation between gut motility and innervation in man. Digestion 11, 392–412 (1974)
Bennett, A., Eley, K. G., Stockley, H. L.: Inhibition of peristalsis in guinea-pig isolated ileum and colon by drugs that block prostaglandin synthesis. Br. J. Pharmacol. 57, 335–340 (1976)
Bertaccini, G.: Active polypeptides of nonmammalian origin. Pharmacol. Rev. 28, 127–177 (1976)
Burnstock, G.: Putinergic nerves. Pharmacol. Rev. 24, 509–581 (1972)
Bury, R. W., Mashford, M. L.: A pharmacological investigation of synthetic substance P on the isolated guinea-pig ileum. Clin. Exp. Pharmacol. Physiol. 4, 453–461 (1977)
Costa, M., Furness, J. B.: The peristaltic reflex: an analysis of the nerve pathways and their pharmacology. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 47–60 (1976)
Del Tacca, M., Soldani, G., Crema, A.: Experiments on the mechanism of action of caerulein at the level of the guinea-pig ileum and colon. Agents and Actions 1, 176–181 (1970)
Del Tacca, M., Soldani, G., Crema, A.: Effects of caerulein on the isolated human ileum. Rendic. Gastroenterol. 6, 165–167 (1974)
Erspamer, V.: Caerulein. Gut 11, 79–87 (1970)
Fontaine, J., van Nueten, J. M., Janssen, P. A. J.: Analysis of the peristaltic reflex in vitro: effects of some antagonists. Arch. Int. Pharmacodyn. Ther. 203, 396–399 (1973)
Frigo, G. M., Lecchini, S., Falaschii, C., del Tacca, M., Crema, A.: On the ability of caerulein to increase propulsive activity in the isolated small and large intestine. Naunyn-Schmiedebergs Arch. Pharmakol. 268, 44–58 (1971)
Gustavsson, S., Johansson, H., Lundqvist, G., Nilsson, F.: Effects of vasoactive intestinal peptide and pancreatic polypeptide on small bowel propulsion in the rat. Scand. J. Gastroent. 12, 993–997 (1977)
Hedqvist, P., von Euler, U. S.: Influence of substance P on the response of guinea-pig ileum to transmural nerve stimulation. Acta Physiol. Scand. 95, 341–343 (1975)
Hökfelt, T., Efendić, S., Hellerström, C., Johansson, O., Luft, R., Arimura, A.: Cellular localisation of somatostatin in endocrine-like cells and neurons of the rat with special references to the A-cells of the pancreatic islets and to the hypothalamus. Acta Endocrinol. 80, Suppl. 200, 5–41 (1975)
Hughes, J., Kosterlitz, H. W., Smith, T. W.: The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues. Br. J. Pharmacol. 61, 639–647 (1977)
Hughes, J., Kosterlitz, H. W., Sosa, R. P.: Enkephalin release from the myenteric plexus of the guinea-pig small intestine in the presence of cycloheximide. Br. J. Pharmacol. 63, 397P (1978)
Johansson, O., Efendić, S., Wisén, O., Uvnäs-Wallensten, K., Luft, R.: Effects of short-time somatostatin infusion on the gastric and intestinal propulsion in humans. Scand. J. Gastroent. 13, 481–483 (1978)
Jorpes, J. E., Mutt, V.: Secretin and cholecystokinin. In: Handbook of exp. pharmacol., Vol. 34: Secretin, cholecystokinin, pancreozymin and gastrin (J. E. Jorpes and V. Mutt, eds.), pp. 1–27. Berlin, Heidelberg, New York: Springer 1973
Katayama, Y., North, R. A.: Does substance P mediate slow synaptic excitation within the myenteric plexus? Nature 274, 387–388 (1978)
Kosterlitz, H. W., Lees, G. M.: Pharmacological analysis of intrinsic intestinal reflexes. Pharmacol. Rev. 16, 301–339 (1964)
Kottegoda, S. R.: An analysis of possible nervous mechanisms involved in the peristaltic reflex. J. Physiol. (Lond.) 200, 687–712 (1969)
Larsson, L.-I., Fahrenkrug, J., Schaffalitzky de Muckadell, O., Sundler, F., Håkanson, R., Rehfeld, J. F.: Localization of vasoactive intestinal polypeptide (VIP) to central and peripheral neurons. Proc. Natl. Acad. Sci. USA 73, 3197–3200 (1976)
Lembeck, F.: Die Beeinflussung der Darmmotilität durch Hydroxytryptamin. Pflügers Arch. ges. Physiol. 265, 567–574 (1958)
Liljedahl, S. O., Matisson, O., Pernow, B.: The effect of substance P on intestinal motility in man. Scand. J. Clin. Lab. Invest. 10, 16–25 (1958)
Mitznegg, P., Domschke, W., Sprugel, N., Domschke, S., Subramaman, N., Wünsch, E., Moroder, L., Demling, L.: Enkephalins inhibit intestinal motility: mode of action. Acta Hepato-Gastroenterol. 24, 119–120 (1977)
Nilsson, G., Larsson, L.-I., Håkanson, R., Brodin, E.: Localization of substance P-like immunoreactivity in mouse gut. Histochemistry 43, 97–99 (9175)
Pearse, A. G. E., Polak, J. M.: Immunocytochemical localization of substance P in mammalian intestine. Histochemistry 41, 373–375 (1975)
Polak, J. M., Pearse, A. G. E., Garaud, J.-C., Bloom, S. R.: Cellular localization of a vasoactive intestinal peptide in the mammalian and avian gastrointestinal tract. Gut 15, 720–724 (1974)
Polak, J. M., Heitz, P., Pearse, A. G. E.: Differential localization of substance P and motilin. Scand. J. Gastroent. 11, Suppl. 39, 39–42 (1976)
Polak, J. M., Bloom, S. R., Sullivan, S. N., Facer, P., Pearse, A. G. E.: Enkephalin-like immunoreactivity in the human gastrointestinal tract. Lancet 1977I, 972–974
Ruppin, H., Sturm, G., Westhoff, D., Domschke, S., Domschke, W., Wünsch, E., Demling, L.: Effect of 13-nle-motilin on small intestinal transit time in healthy subjects. Scand. J. Gastroent. 11, Suppl. 39, 85–88 (1976)
Schaumann, W.: The influence of atropine and morphine on the liberation of acetylcholine from the guinea-pig's intestine. Nature 178, 1121–1122 (1956)
Schiller, P. W., Lipton, A., Horrobin, D. F., Bodanszky, M.: Unsulfated C-terminal 7-peptide of cholecystokinin: a new ligand of the opiate receptor. Biochem. Biophys. Res. Commun. 85, 1332–1338 (1978)
Schultzberg, M., Dreyfus, C. F., Gershon, M. D., Hökfelt, T., Elde, R. P., Nilsson, G., Said, S., Goldstein, M.: VIP-, enkephalin-, substance P-, and somatostatin-like immunoreactivity in neurons intrinsic to the intestine: immunohistochemical evidence from organotypic tissue cultures. Brain Res. 155, 239–248 (1978)
Trendelenburg, P.: Physiologische und pharmakologische Versuche über die Dünndarmperistaltik. Naunyn-Schmiedeberg's Arch. Exp. Path. Pharmakol. 81, 55–129 (1917)
Tyrode, M. V.: The mode of actions of some purgative salts. Arch. Int. Pharmcodyn. Ther. 20, 205–243 (1910)
Van Nueten, J. M., Geivers, H., Fontaine, J., Janssen, P. A. J.: An improved method for studying peristalsis in the isolated guineapig ileum. Arch. Int. Pharmacodyn. Ther. 203, 411–414 (1973)
Van Nueten, J. M., van Ree, J. M., Vanhoutte, P. M.: Inhibition by met-enkephalin of peristaltic activity in the guinea-pig ileum, and its reversal by naloxone. Eur. J. Pharmacol. 41, 341–342 (1977)
Wood, J. D., Mayer, C. F.: Slow synaptic excitation mediated by serotonin in Auerbach's plexus. Nature 276, 836–837 (1978)
Zetler, G.: Enkephalins as antagonists of cholecystokinin-like peptides. Naunyn-Schmiedeberg's Arch. Pharmacol. 207, R51 (1979)
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Holzer, P., Lembeck, F. Effect of neuropeptides on the efficiency of the peristaltic reflex. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 257–264 (1979). https://doi.org/10.1007/BF00505942
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DOI: https://doi.org/10.1007/BF00505942