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Pharmacological characterisation of neurokinin receptors mediating anion secretion in rat descending colon mucosa

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Summary

Substance P(SP), neurokinin A (NKA), neurokinin B (NKB), [Sar9, Met (O2)11]-SP (SMSP), senktide, [βAla8]-NKA(4–10) and neuropeptide γ (NPγ) all stimulate secretory responses in rat descending colon mucosa under voltage clamp conditions. Secretory responses (measured as short circuit current under voltage clamp conditions) were transient and those evoked by SP, SMSP, NKA and senktide were significantly reduced by pretreating tissues with the chloride channel blocker, diphenylamine carboxylate (DPC). Concentration-response curves showed varying degrees of sensitivity to tetrodotoxin (TTX). Senktide-induced secretion was virtually abolished by TTX, while NPγ and [βAla8]-NKA(4–10) were not significantly altered. Rightward shifts of concentration-response curves were observed for SMSP, NKA and SP in TTX treated preparations compared with controls. NKA response curves in the presence of TTX were further inhibited by MEN10,207 and CP-96,345. GR71251, GR82334 and CP-96,345 all inhibited SMSP secretory responses with pA2 values of 5.8, 6.5 and 6.9 respectively. In conclusion three types of neurokinin receptor exist in preparations of rat colon mucosa and their relative location within neuronal and epithelial surfaces are discussed.

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References

  • Bartho L, Santicioli P, Patacchini R, Maggi CA (1992) Tachykininergic transmission to the circular muscle of the guinea-pig ileum: evidence for the involvement of NK2 receptors. Br J Pharmacol 105:805–810

    Google Scholar 

  • Beresford IJM, Birch PJ, Hagan RM, Ireland SJ (1991) Investigation into species variants in tachykinin NK1 receptors by use of the nonpeptide antagonist, CP-96,345. Br J Pharmacol 104:292–293

    Google Scholar 

  • Black JL, Diment LM, Alouan LA, Johnson PRA, Armour CL, Badgery-Parker T, Butcher E (1992) Tachykinin receptors in rabbit airways-characterisation by functional, autoradiographic and binding studies. Br J Pharmacol 107:429–436

    Google Scholar 

  • Bridges RJ, Rummel W Simon B (1983) Forskolin induced Cl secretion across the isolated mucosa of rat colon descendens. Naunyn-Schmiedeberg's Arch Pharmacol 323:355–360

    Google Scholar 

  • Brodin E, Sjölund K, Håkanson R, Sundler F (1983) Substance P —containing fibres are numerous in human but not in feline intestinal mucosa. Gastroenterology 85:557–564

    Google Scholar 

  • Burcher E, Shults CW, Buck SH, Chase TN, O'Donohue TL (1984) Autoradiographic distribution of substance K binding sites in rat gastrointestinal tract: a comparison with substance P. Eur J Pharmacol 102:561–562

    Google Scholar 

  • Burcher E, Buck SH, Lovenberg W, O'Donohue TL (1986) Characterisation and autoradiographic localisation of multiple tachykinin binding sites in gastrointestinal tract and bladder. J Pharmacol Exp Ther 236:819–831

    Google Scholar 

  • Burcher E, Bornstein JC (1988) Localisation of substance P binding sites in submucous plexus of guinea-pig ileum, using whole mount autoradiography. Synapse 2:232–239

    Google Scholar 

  • Chang FY, Sharp D, Ouyang A (1991) Multiple neurokinin receptor subtypes are present in the colon of the cat and rat. Ann NY Acad Sci. 632:374–376

    Google Scholar 

  • Cox HM; Cuthbert AW, Hakanson R, Wahlestedt C (1988) The effect of NPY and PYY on electrogenic ion transport in rat intestinal epithelia. J Physiol 398:65–80

    Google Scholar 

  • Cox HM, Cuthbert AW (1990) The effects of neuropeptide Y and its fragments upon basal and electrically stimulated ion secretion in rat jejunum mucosa. Br J Pharmacol 101:247–252

    Google Scholar 

  • Di Stefano A, Wittner M, Schlatter E, Lang HJ, Englert H, Greger R (1985) Diphenylamine-2-carboxylate, a blocker of the Cl-conductance pathway in Cl-transporting epithelia. Pflügers Arch 405 (Suppl 1):S95-S100

    Google Scholar 

  • Ekblad E, Winther R, Ekman R, Hakanson R, Sundler F (1987) Projections of peptide-containing neurones in rat small intestine. Neuroscience 20:169–188

    Google Scholar 

  • Ekblad E, Ekman R, Hakanson R, Sundler F (1988) Projections of peptide-containing neurones in rat colon. Neuroscience 27:655–674

    Google Scholar 

  • Fong TM, Cascieri MA, Hong Y, Bansal A, Swain C, Strader CD (1993) Amino-aromatic interaction between histidine 197 of the neurokinin-1 receptor and CP 96345. Nature 362:350–353

    Google Scholar 

  • Gether U, Johansen TE, Snider RM, Lowe JA, Nakanishi S, Schwartz TW (1993) Different binding epitopes on the NK1 receptor for substance P and a non-peptide antagonist. Nature 362:345–348

    Google Scholar 

  • Guard S, Watson SP (1987) Evidence for neurokinin-3 receptor-mediated tachykinin release in the guinea-pig ileum. Eur J Pharmacol 144:409–412

    Google Scholar 

  • Guard S, Watson SP (1991) Tachykinin receptor types: classification and membrane signalling mechanisms. Neurochem Int 18:149–165

    Google Scholar 

  • Kachur JF, Miller RJ, Field M, Rivier J (1982) Neurohumoral control of ileal electrolyte transport — II Neurotensin and substance P. J Pharmacol Exp Ther 220:456–463

    Google Scholar 

  • Kage R, McGregor GP, Thim L, Conlon JM (1988) Neuropeptide γ: a peptide isolated from rabbit intestine that is derived from γ-preprotachykinin. J Neurochem 50:1412–1417

    Google Scholar 

  • Keast JR, Furness JB, Costa M (1985) Different substance P receptors are found on mucosal epithelial cells and submucous neurons of the guinea-pig small intestine. Naunyn-Schmiedeberg's Arch Pharmacol 329:382–387

    Google Scholar 

  • Kuwahara A, Cooke HJ (1990) Tachykinin-induced anion secretion in guinea-pig distal colon: role of neural and inflammatory mediators. J Pharmacol Exp Ther 252:1–7

    Google Scholar 

  • Legat FJ, Griesbacher T, Lembeck F (1992) CP-96,345, a non-peptide antagonist of substance P: I Effects on the actions mediated by substance P and related tachykinins on the guinea-pig ileum and rabbit jejunum. Naunyn-Schmiedeberg's Arch Pharmacol 346:315–322

    Google Scholar 

  • Maggi CA, Patacchini R, Giuliani S, Rovers S, Dion S, Regoli D, Giachetti A, Meli A (1990) Competitive antagonists discriminate between NK2 receptor subtypes. Br J Pharmacol 100:588–592

    Google Scholar 

  • Mantyh PW Gates T, Mantyh CR, Maggio JE (1989) Autoradiographic localisation and characterisation of tachykinin receptor binding sites in rat brain and peripheral tissues. J Neuroscience 9:258–279

    Google Scholar 

  • Mantyh PW, Mantyh CR, Gates T, Vigna SR, Maggio JE (1988) Receptor binding sites for substance P and substance K in the canine and gastrointestinal tract and their possible role in inflammatory bowel disease. Neuroscience 25:817–837

    Google Scholar 

  • Nau R, Schafer G. Conlon JM (1985) Proteolytic inactivation of substance P in the epithelial layer of the intestine. Biochem Pharmacol 34:4019–4023

    Google Scholar 

  • Nawa H, Kotani H, Nakanishi S (1984) Tissue specific generation of two preprotachykinin mRNAs from one gene by alternative RNA splicing. Nature 312:729–734

    Google Scholar 

  • Parsons AM, Seybold VS, Chandan R, Vogt J, Larson AA, Murray CR, Soldani G, Brown DR (1992) Neurokinin receptors and mucosal ion transport in porcine jejunum. J Pharmacol Exp Ther 261: 1213–1221

    Google Scholar 

  • Reddix RA, Cooke HJ (1992) Neurokinin 1 receptors mediate substance P induced changes in ion transport in guinea-pig ileum. Regul. Peptides 39:215–225

    Google Scholar 

  • Snider RM, Constantine JW Lowe JA, Longo KP, Lebel WS, Woody HA, Drozda SE, Desai MJ, Vinick FJ, Spencer RW Hess H-J (1991) A potent nonpeptide antagonist of the substance P (NK1) receptor. Science 251:435–437

    Google Scholar 

  • Sternini C, Anderson K, Frankz G, Krause J, Brecha N (1989) Expression of SP/NKA-encoding preprotachykinin messenger ribonucleic acids in the rat enteric nervous system. Gastroenterology 97: 348–356

    Google Scholar 

  • Tatemoto K, Lundberg JM, Jörnvall H, Mutt V (1985) Neuropeptide K: isolation, structure and biological activities of a novel brain tachykinin. Biochem Biophys Res Commun 128:947–953

    Google Scholar 

  • Walling MW, Brasitus TA, Kimberg DV (1977) Effects of calcitonin and substance P on the transport of Ca, Na and Cl across rat ileum in vitro. Gastroenterology 73:89–94

    Google Scholar 

  • Willard AL (1990) Substance P mediates synaptic transmission between rat myenteric neurones in cell culture. J Physiol 426:453–471

    Google Scholar 

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Correspondence to H. M. Cox at the above address

K. G. and S. Y. were project students with H. M. C. in the Department of Pharmacology, University of Cambridge. S. Y. was also a Wellcome Trust Vacation Scholar

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Cox, H.M., Tough, I.R., Grayson, K. et al. Pharmacological characterisation of neurokinin receptors mediating anion secretion in rat descending colon mucosa. Naunyn-Schmiedeberg's Arch Pharmacol 348, 172–177 (1993). https://doi.org/10.1007/BF00164795

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  • DOI: https://doi.org/10.1007/BF00164795

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