Summary
-
1.
The effects on cutaneous vascular permeability of substance P. physalaemin, eledoisinrelated peptide, bradykinin, somatostatin, neurotensin, methionine enkephalin, vasoactive intestinal peptide, cholecystokinin and pentagastrin were investigated in rats using a quantitative Evans blue dye leakage technique to estimate plasma exudation.
-
2.
Substance P, physalaemin, eledoisin-related peptide, bradykinin, somatostatin and neurotensin produced plasma exudation, neurotensin being the most potent of the peptides tested. The high potency of neurotensin would suggest that this peptide might play a role in local regulation of the microcirculation in some organs.
-
3.
Pretreatment of rats with mepyramine and methysergide significantly reduced responses to substance P (5×10−9 mol) and neurotensin (5×10−9 mol).
-
4.
Responses to neurotensin (5×10−11 and 5×10−10 mol) were almost abolished by mepyramine and methysergide and also be pretreatment of skin sites with compound 48/80. The response to substance P (5×10−10 mol) was not reduced by compound 48/80 but was reduced by mepyramine and methysergide. The response to substance P (5×10−9 mol) was reduced by both treatments but was not abolished.
-
5.
No significant interactions were found between any of the peptide combinations tested.
-
6.
The effect of neurotensin was significantly potentiated by 5-hydroxytryptamine, PGE1 and ATP.
-
7.
It was concluded that substance P has both a direct action to increase vascular permeability in rat skin and an indirect action mediated by amine release from mast cells, whereas neurotensin has mainly an indirect amine-releasing action.
Similar content being viewed by others
References
Arvier, P. T., Chahl, L. A., Ladd, R. J.: Modification by capsaicin and compound 48/80 of dye leakage induced by irritants in the rat. Br. J. Pharmacol. 59, 61–68 (1977)
Brown, M., Villarreal, J., Vale, W.: Neurotensin and substance P: Effects on plasma insulin and glucagon levels. Metabolism 25 (Suppl 1), 1459–1461 (1976)
Carraway, R., Leeman, S. E.: The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami. J. Biol. Chem. 248, 6854–6861 (1973)
Carraway, R., Leeman, S. E.: Characterization of radioimmunoassayable neurotensin in the rat. Its differential distribution in the central nervous system, small intestine, and stomach. J. Biol. Chem. 251, 7045–7052 (1976)
Chahl, L. A.: Interactions of substance P with putative mediators of inflammation and ATP. Eur. J. Pharmacol. 44, 45–49 (1977)
Elde, R., Hökfelt, T., Johansson, O., Terenius, L.: Immunohistochemical studies using antibodies to leucine-enkephalin: initial observations on the nervous system of the rat. Neuroscience 1, 349–351 (1976)
Garcia Leme, J., Hamamura, L.: Formation of a factor increasing vascular permeability during electrical stimulation of the saphenous nerve in rats. Br. J. Pharmacol. 51, 383–389 (1974)
Hägermark, O., Hökfelt, T., Pernow, B.: Flare and itch induced by substance P in human skin. J. Invest. Dermatol. 71, 233–235 (1978)
Harada, M., Takeuchi, M., Fukao, T., Katagiri, K.: A simple method for the quantitative extraction of dye extravasated into the skin. J. Pharm. Pharmacol. 23, 218–219 (1971)
Hökfelt, T., Kellerth, J.-O., Nilsson, G., Pernow, B.: Experimental immunohistochemical studies on the localization and distribution of substance P in cat primary sensory neurons. Brain Res. 100, 235–252 (1975a)
Hökfelt, T., Elde, R., Johansson, O., Luft, R., Arimura, A.: Immunohistochemical evidence for the presence of somatostatin, a powerful inhibitory peptide, in some primary sensory neurons. Neurosci. Lett. 1, 231–235 (1975b)
Jancsó, N., Jancsó-Gábor, A., Szolcsányi, J.: Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br. J. Pharmacol. 31, 138–151 (1967)
Johnson, A. R., Erdös, E. G.: Release of histamine from mast cells by vasoactive peptides. Proc. Soc. Exp. Biol. Med. 142, 1252–1256 (1973)
Kiernan, J. A.: The involvement of mast cells in vasodilatation due to axon reflexes in injured skin. Q. J. Exp. Physiol. 57, 311–317 (1972)
Larsson, L.-I., Fahrenkrug, J., Schaffalitzky de Muckadell, O., Sundler, F., Hákanson, R., Rehfeld, J. F.: Localization of vasoactive intestinal polypeptide (VIP) to central and peripheral neurons. Proc. Natl. Acad. Sci. USA. 73, 3197–3200 (1976)
Larsson, L.-I., Rehfeld, J. F.: Localization and molecular heterogeneity of cholecystokinin in the central and peripheral nervous system. Brain Res. 165, 201–218 (1979)
Lazarus, L. H., Brown, M. R., Perrin, M. H., Rivier, J. E.: Neurotensin: mast cell receptor binding with comparison to biological activity. Fed. Proc. 36, 1015 (1977)
Lembeck, F.: Zur Frage der zentralen Übertragung afferenter Impulse. III. Mitteilung. Das Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks. Naunyn-Schmiedeberg's Arch. exp. Pathol. Pharmakol. 219, 197–213 (1953)
Lembeck, F., Gamse, R., Juan, H.: Substance P and sensory nerve endings. In: Substance P (U. S. von Euler, B. Pernow, eds.), pp. 169–181. New York: Raven Press 1977
Uhl, G. R., Goodman, R. R., Snyder, S. H.: Neurotensin-containing cell bodies, fibers and nerve terminals in the brain stem of the rat: immunohistochemical mapping. Brain Res. 167, 77–91 (1979)
Author information
Authors and Affiliations
Additional information
A preliminary report of this work was given at the 12th annual meeting of the Australasian Society of Clinical and Experimental Pharmacologists, December, 1978
Rights and permissions
About this article
Cite this article
Chahl, L.A. The effect of putative peptide neurotransmitters on cutaneous vascular permeability in the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 309, 159–163 (1979). https://doi.org/10.1007/BF00501224
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00501224