Summary
Preparations of rat descending colon mucosa have been used to record changes in short circuit current (SCC) under voltage clamp conditions. When added to the basolateral compartment capsaicin (8-methyl-N-vanillyl-6-nonenamide, 0.1-3 μM) caused an initial transient increase in SCC, followed by a more prolonged reduction in SCC, that lasted for 20–30 min.
Repeated applications of 3 μM capsaicin caused desensitisation of the initial secretory response. The antisecretory effects (i. e. reduction in SCC from the original baseline) remained, although they were significantly reduced. In some preparations described as “non-responders”, 3 μM capsaicin did not elicit a secretory response. No desensitisation of the remaining antisecretory responses was observed in these tissues; in fact these reductions in SCC were consistently larger than those from tissues which responded with a secretory response.
Tetrodotoxin (100 nM), hexamethonium (10 μM), and yohimbine (50 μM) had no significant effect upon either secretory or antisecretory responses. Ruthenium red (10 μM) abolished the secretory response to 3 μM capsaicin, but had no effect upon the antisecretory responses. Pretreatment of the tissues with 1 μM substance P(SP) resulted in significant desensitisation to the peptide and abolished the secretory response to 3 μM capsaicin. The antisecretory responses remained, and were significantly larger compared with responses from control tissues.
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References
Baccaglini PI, Hogan PC (1983) Some rat sensory neurones in culture express characteristics of differentiated pain sensory cells. Proc Natl Acad Sci USA 80:594–598
Bridges RJ, Rummel W, Simon B (1983) Forskolin induced chloride secretion across the isolated mucosa of rat colon descendens. Naunyn-Schmiedeberg's Arch Pharmacol 323:355–360
Chang EB, Field M, Miller RJ (1982) {α2-Adrenergic receptor regulation of ion transport in rabbit ileum}. Am J Physiol0 242:G237-G242
Cox HM, Cuthbert AW (1989) Antisecretory activity of the α2-adrenoceptor agonist, xylazine in rat jejunal epithelium. Naunyn-Schmiedeberg's Arch Pharmacol 339:669–674
Cox HM, Cuthbert AW, Häkanson R, Wahlestedt C (1988) The effect of NPY and peptide YY on electrogenic ion transport in rat intestinal epithelium. J Physiol 398:65–80
Cox HM, Ferrar JA, Cuthbert AW (1989) Effects of α- and β-CGRPs upon ion transport in rat descending colon. Br J Pharmacol 97:996–998
Dray A, Forbes CA, Burgess GM (1990) Ruthenium red blocks the capsaicin-induced increase in intracellular calcium and activation of membrane currents in sensory neurones as well as the activation of peripheral nociceptors in vitro. Neurosci Lett 110:52–59
Dunning BE, Taborsky GJ (1987) CGRP: a potent and selective stimulator of gastrointestinal somatostatin secretion. Endocrinology 120:1774–1781
Ekblad E, Ekman R, Häkanson R, Sundler F (1988) Projections of peptide-containing neurones in rat colon. Neuroscience 27:655–674
Ferrar JA, Cuthbert AW, Cox HM (1990) The antisecretory effects of somatostatin in rat descending colon. Eur J Pharmacol 184:295–303
Franco-Cereceda A, Henke H, Lundberg JM, Petermann JB, Hökfelt T, Fischer JA (1987) CGRP in capsaicin-sensitive, substance P-immunoreactive sensory neurones in animals and man distribution and release by capsaicin. Peptides 8:
Gamse R, Molnar A, Lembeck F (1979) Substance P release from spinal cord slices by capsaicin. Life Sci 25:629–636
Gamse R, Lackner D, Gamse G, Leeman SE (1981) Effect of capsaicin pretreatment on capsaicin-evoked release of immunoreactive somatostatin and substance P from primary sensory neurones. Naunyn-Schmiedeberg's Arch Pharmacol 316:38–41
Gates TS, Zimmerman RP, Mantyh CR, Vigna SR, Maggio JE, Welton ML, Passaro EP, Mantyh PW (1988) Substance P and substance K receptor binding sites in the human gastrointestinal tract: localisation by autoradiography. Peptides 9:1207–1219
Holzer P, Gamse R, Lembeck F (1980) Distribution of substance P in the rat gastrointestinal tract — lack of effect of capsaicin pretreatment. Eur J Pharmacol 61:303–307
Jessell TM, Iversen LL, Cuello AC (1978) Capsaicin-induced depletion of substance P from primary sensory neurones. Brain Res 152:183–188
Kachur JF, Miller RJ, Field M, Rivier J (1982) Neurohumoral control of ilea] electrolyte transport — II. Neurotensin and substance P. J Pharm Exp Ther 220:456–463
Maggi CA, Meli A, Santicioli P (1987) Four motor effects of capsaicin on guinea-pig distal colon. Br J Pharmacol 90:651–660
Maggi CA, Santicioli P, Geppetti P, Giuliani S, Patacchini R, Frilli S, Grassi J, Meli A (1987) Involvement of a peripheral site of action in the early phase of neuropeptide depletion following capsaicin desensitisation. Brain Res 436:402–406
Mantyh PW, Mantyh CR, Gates T, Vigna SR, Maggio JE (1988) Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease. Neuroscience 25:817–837
Mantyh PW, Catton MD, Boehmer CG, Welton ML, Passaro EP, Maggio JE, Vigna SR (1989) Receptors for sensory neuropeptides in human inflammatory diseases — implications for the effector role of sensory neurones. Peptides 10:627–645
Marsh SJ, Stansfield CE, Brown DA, Davey R, McCarthy D (1987) The mechanism of action of capsaicin on sensory C-type neurones and their axons in vitro. Neuroscience 23:275–289
Mulderry PK, Ghatei MA, Spokes RA, Jones PM, Pierson AM, Hamid QA, Kanse S, Amara SG, Burrin JM, Legon S, Polak JM, Bloom SR (1988) Differential expression of α-CGRP and β-CGRP by primary sensory neurones and enteric autonomic neurones in the rat. Neuroscience 25:195–205
Nagy JI, Hunt SP, Iversen LL, Emson PC (1981) Biochemical and anatomical observations on the degeneration of peptide-containing primary afferent neurones after neonatal capsaicin. Neuroscience 6:1923–1934
Perkins MN, Forster PL, Dray A (1988) The involvement of afferent nerve terminals in the stimulation of ion transport by bradykinin in rat isolated colon. Br J Pharmacol 94:47–54
Petersson G, Malm L, Ekman R, H»kanson R (1989) Capsaicin evokes secretion of nasal fluid and depletes substance P and calcitonin gene-related peptide from the nasal mucosa in the rat. Br J Pharmacol 98:930–936
Quaglio MP, Romagnolo M, Sandri-Caviccini G (1971) Determination of the active principle of Capsicum (red pepper). Farmacol Ed Prat 26:349–355
Skofitsch G, Jacobowitz DM (1985) Calcitonin gene-related peptide coexists with substance P in capsaicin-sensitive neurones and sensory ganglia of the rat. Peptides 6:747–754
Sternini C, Reeve JR, Brecha N (1987) Distribution and characterisation of CGRP immunoreactivity of the digestive system of normal and capsaicin-treated rats. Gastroenterology 93:852–862
Yamatini T, Kadowaki S, Chiba T, Abe H, Chihara K, Fukase M, Fujita T (1986) CGRP stimulates somatostatin release from isolated perfused rat stomach. Endocrinology 118:2144–2145
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Yarrow, S., Ferrar, J.A. & Cox, H.M. The effects of capsaicin upon electrogenic ion transport in rat descending colon. Naunyn-Schmiedeberg's Arch Pharmacol 344, 557–563 (1991). https://doi.org/10.1007/BF00170652
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DOI: https://doi.org/10.1007/BF00170652