Role of tachykinins in the control of pancreatic secretion and circulation

• Autorzy: Pawlik W W , Konturek S.J. , Gustaw P. , Czarnobilski K. , Sendur R. , Jaworek J. , Yanaihara N.
• Języki publikacji: EN

Abstrakty

EN

Tachykinins (TK) are family of peptides including substance P (SP), substance K (SK) and neuromedin K (NK) that have been found in the nerves of the gastrointestinal tract and proposed to act as neurotransmitters to affect the motor, secretory and circulatory functions of the gut, but little is known about their action on the pancreas. In this study three series of tests were carried out to determine the action of SP, SK and NK on pancreatic secretion in conScious dogs and amylase release from the dispersed rat pancreatic acini and to correlate the alterations in pancreatic secretory and circulatory effects of TK in anesthetized dogs. SP, SK and NK infused i. v. in graded doses (0.12-1.0 µg/kg per h) in conscious dogs stimulated pancreatic protein outputs reaching, respectively, 38% and 23% of the maximal response to CCK (40 pmol/kg per h). HCO₃ outputs were also significantly increased but the highest response did not exceed about 5% of secretin (328 pmol/kg per h) maximum. Cholinergic blockade by atropine abolished the pancreatic responses to tachykinins. When added at various concentrations (10⁻¹¹ -10⁻⁷ M) to the incubation medium of rat dispersed pancreatic acini, SK, SP and NK increased in concentration-dependent manner the release of amylase from the resting pancreatic acini and augmented the enzyme release induced by CCK-8 and by urecholine. In anesthetized dogs infused with a background dose of secretin (82 pmol/kg per h), addition of SP, SK and NK caused an immediate and dose-dependent increase in the pancreatic blood flow, oxygen consumption and pancreatic secretion accompanied by a dose-dependent decrease in arterial blood pressure. This study shows that TK are potent pancreatic circulatory stimulants and moderate secretagogues both in vivo and in vitro, acting, at least in part, via cholinergic pathway.

Słowa kluczowe

EN

neuromedin K; pancreas; tachykinin; blood flow; oxygen consumption; circulation; secretion; cholecystokinin; substance K; substance P

• Wydawca: -
• Czasopismo: Journal of Physiology and Pharmacology
• Rocznik: 1992
• Tom: 43
• Numer: 1
• Opis fizyczny: p.43-57,fig.

Twórcy

autor

Pawlik W W

• Medical Academy, ul.Grzegorzecka 16, 31-531 Krakow, Poland

autor

Konturek S.J.

autor

Gustaw P.

autor

Czarnobilski K.

autor

Sendur R.

autor

Jaworek J.

autor

Yanaihara N.

Bibliografia

• 1. Erspamer V. The tachykinin peptide family. Trends NeuroSci 1981; 4: 267-269.
• 2. Kanagawa K, Minamino N, Fucuda A, Matsuo H. Neuromedin K: a novel mammalian tachykinin indentified in porcine spinal cord. Biochem Biophys Res Commun 1983; 14: 533-540.
• 3. Kimura S, Okada M, Sugita Y, Kanazawa I, Munekata E. Novel neuropeptides, neurokinin alpha and beta isolated from porcine spinal cord. Proc Jap Acad. Sci. 1983; В 59: 101-104.
• 4. Hunter JC, Maggio JE. Pharmacological characterization of a novel tachykinin, isolated from mammalian spinal cord. Eur J Pharmacol 1984; 97: 159-160.
• 5. Euler VS, Gaggum JH. An unidentified depressor substance in certain tissue extracts. J Physiol London 1931; 72: 74-84.
• 6. Kuwahara A, Ishikawa T, Mikamis S, Yanaihara N. Distribution of neurons containing immunoreactivity for gastrin-releasing peptide (GRP), substance P and vasoactive intestinal polypeptide (VIP) in the rat gastric wall. Biomed Res 1983; 4: 473-478.
• 7. Schultzberg M, Hokfelt T, Nilsson G, et al. Distribution of peptide and catecholamine-containing neurons in the gastrointestinal tract of rat and guinea-pig: immunohistochemical studies with antisera to substance P, vasoactive intestinal polypeptide, enkephalins, somatostatin, gastrin, cholecystokinin, neurotensin and dopamine beta-hydrolase. Neuroscience 1980; 5: 689-744.
• 8. Kimura S, Goto K, Ogawa T, Sugita Y, Kanazawa I. Pharmacological characterization of novel mammalian tachykinins, neurokinin alfa and neurokinin beta. Neurosci Res 1984; 2: 97-104.
• 9. Pernow B. Substance P. Pharmacol Rev 1983; 35: 85-141.
• 10. Thulin L, Holm I. Effect of substance P on the flow of hepatic bile and pancreatic juice. In: Substance P, New York, Raven, 1977; pp. 247-251.
• 11. Konturek SJ, Jaworek J, Tasler J, Cieszkowski M, Pawlik W. Effect of substance P and its C-terminal hexapeptide on gastric and pancreatic secretion in the dog. Am J Physiol 1981; 241, G74-G81.
• 12. Gardner JD, Jensen RT. Secretagogue receptors on pancreatic acinar cells. Physiology of the Gastrointestinal Tract. Ed. by L. R. Johnson Raven Press, New York 1987, pp. 1109-1127.
• 13. Kuwahara A, Yanaihara N. Action of the newly discovered mammalian tachykinins, substance K, neuromedin K, on gastroduodenal motility of anesthetized dogs. Reg Pept 1987; 17: 221-228
• 14. Konturek SJ, Konturek P, Bielański W, Szewczyk K. CCK receptors in release of pancreatic polypeptide (PP) in dogs. Dig Dis Sci 1989; 34: 849-856.
• 15. Konturek SJ, Jaworek J. Cieszkowski M, Pawlik W, Kania J, Bloom SR. Comparison of effects of neurotensin and fat on pancreatic stimulation in dogs. Am J Physiol 1983; 244: G590-G598.
• 16. Konturek SJ, Tasler J, Cieszkowski M, Coy DH Schally AV. Effect of growth hormone release-inhibiting hormone on gastric secretion, mucosal blood flow and serum gastrin. Gastroenterology 1976; 70: 737-741.
• 17. Konturek SJ, Tasler J, Bilski J, Konturek J, Bielański W. Studies on the localization of secretin release from canine intestine. Digestion 1986; 34: 207-215.
• 18. Konturek SJ, Swierczek S, Kwiecień N, et al. Gastric secretory and plasma hormonal reponses to sham-feeding of varying duration in patients with gastroduodenal ulcer. Gut 1981; 22: 1003-1010.
• 19. Amsterdam A, Solomon ТЕ, Jamieson JD. Sequential dissociation of exocrine pancreas into lobules, acini and individual cells. Methods Cell Biol 1978; 20: 362-376.
• 20. Bernfeld P. Amylases alpha and beta. In Methods in Enzymology (Academic, New York) 1955; pp. 139-148.
• 21. Konturek SJ, Yanaihara N, Pawlik W, Jaworek J, Szewczyk K. Comparison of helodermin, VIP and PHI in pancreatic secretion and blood flow in dogs, Reg Pept 1989; 24: 155-166.
• 22. Shepherd AP, Burgar CG. A solid-state arteriovenous oxygen difference analyzer for flowing whole blood. Am J Physiol 1977; 232: H437-H440.
• 23. Domschke S, Konturek SJ, Domschke W, et al. Cyclic-АМР and pancreatic bicarbonate secretion in response to secretin in dogs. Proc Soc Exp Biol Med 1975; 150: 773-779.
• 24. Sjodin L, Conlon TP, Gustavson C, Uddholm K. Interaction of substance P with dispersed pancreatic acinar cells from the guinea pig. Stimulation of calcium outflux, accumulation of cyclic GMP and amylase release. Acta Physiol Scand 1980; 109: 107-110.
• 25. Jensen RT, Gardner JD. Interaction of physalaemin, substance P and eledoisin with specific membrane receptors on pancreatic acinar cells. Proc Natl Acad Sci USA, 1979; 76: 5679-5683.
• 26. Uhlemann ER, Rottman AJ, Gardner JD. Actions of peptides isolated from amphibian skin on amylase from dispersed pancreatic acini. Am J Physiol 1979; 236: E571-E576.
• 27. Sonquet JC, Grider JR, Bitar KN, Makhlouf GM. Receptors for mammalian tachykinins on isolated smooth muscle cells. Am J Physiol 1985; 248: G533-G538.
• 28. Thor P, Sendur R. Konturek SJ. Influence of substance P on myoelectrical activity of the small bowel. Am J Physiol 1982; 243: G493-G496.
• 29. Holtzer P, Lembeck F. Neurally mediated contraction of ileal longitudinal muscle by substance P. NeuroSci Lett 1980; 17: 101-105.
• 30. Beglinger C, Taylor IL, Grossman MI, Solomon ТЕ. Pancreatic polypeptide release: Role of stimulants of exocrine pancreatic secretion in dogs. Gastroenterology. 1984; 87: 530-536.
• 31. Kvietys PR, Mc Lendon IM, Bulkley GB, Perry MA, Granger CN. Pancreatic circulation: intrinsic regulation. Am J Physiol 1982; 242: G596-G602.
• 32. Chahl LA, Walker SB. Responses of the rat cardiovascular system to substance P, neurotensin and bombesin. life Sci 1981; 29: 2009-2015.
• 33. Beijer HJM, Haas AHJ, Charbon GA. Pancreatic O₂ consumption and CO₂ output during secretin-induced exocrine secetion from the panreas in the anesthetized dog. Pflügers Arch 1984; 400: 318-323.