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. 1993 Mar;108(3):694–699. doi: 10.1111/j.1476-5381.1993.tb12863.x

Effects of interactions of naturally-occurring neuropeptides on blood flow in the rat knee joint.

F Y Lam 1, W R Ferrell 1
PMCID: PMC1908032  PMID: 7682133

Abstract

1. Changes of blood flow in the rat knee joint, measured by laser Doppler flowmetry, were produced by topical application of naturally-occurring neuropeptides to the joint capsule. 2. Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) all produced dose-dependent transient vasodilatation of the rat knee joint microvasculature. NKB showed significantly smaller vasodilator responses compared to SP and NKA which were similar in their potencies. 3. Calcitonin gene-related peptide (CGRP) produced dose-dependent vasodilatation which was more pronounced than that produced by the neurokinins. The rank order of potency was: CGRP > SP = NKA > NKB. The vasodilator effect of CGRP was also more prolonged and this extended phase was abolished by co-administration of SP. 4. Cross-tachyphylaxis was not observed with the different neurokinins, but SP and NKA showed novel antagonistic effects on NKB-induced vasodilatation. 5. Co-administration of 1 nmol of the specific NK1 receptor antagonist, CP-96345, with 1 nmol of each of the neurokinins produced significant inhibition of the vasodilator response to SP but did not affect vasodilator responses to NKA and NKB. Co-administration of CP-96345 with the neurokinins plus superfusion of the rat knee joint with a solution containing 0.1 mM CP-96345 further reduced the vasodilator responses to SP but again the vasodilator responses to NKA and NKB were not significantly altered. 6. The results suggest that multiple neurokinin receptor types may be present in the rat knee joint which could mediate the vasodilator responses of the different neurokinins.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Andrews P. V., Helme R. D. Tachykinin-induced vasodilatation in rat skin measured with a laser-Doppler flowmeter: evidence for receptor-mediated effects. Regul Pept. 1989 Jun-Jul;25(3):267–275. doi: 10.1016/0167-0115(89)90175-4. [DOI] [PubMed] [Google Scholar]
  2. Andrews P. V., Helme R. D., Thomas K. L. NK-1 receptor mediation of neurogenic plasma extravasation in rat skin. Br J Pharmacol. 1989 Aug;97(4):1232–1238. doi: 10.1111/j.1476-5381.1989.tb12583.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beaujouan J. C., Torrens Y., Viger A., Glowinski J. A new type of tachykinin binding site in the rat brain characterized by specific binding of a labeled eledoisin derivative. Mol Pharmacol. 1984 Sep;26(2):248–254. [PubMed] [Google Scholar]
  4. Brain S. D., Williams T. J. Interactions between the tachykinins and calcitonin gene-related peptide lead to the modulation of oedema formation and blood flow in rat skin. Br J Pharmacol. 1989 May;97(1):77–82. doi: 10.1111/j.1476-5381.1989.tb11926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brain S. D., Williams T. J., Tippins J. R., Morris H. R., MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator. Nature. 1985 Jan 3;313(5997):54–56. doi: 10.1038/313054a0. [DOI] [PubMed] [Google Scholar]
  6. Buck S. H., Burcher E., Shults C. W., Lovenberg W., O'Donohue T. L. Novel pharmacology of substance K-binding sites: a third type of tachykinin receptor. Science. 1984 Nov 23;226(4677):987–989. doi: 10.1126/science.6095447. [DOI] [PubMed] [Google Scholar]
  7. Erspamer G. F., Erspamer V., Piccinelli D. Parallel bioassay of physalaemin and kassinin, a tachykinin dodecapeptide from the skin of the African frog Kassina senegalensis. Naunyn Schmiedebergs Arch Pharmacol. 1980 Feb;311(1):61–65. doi: 10.1007/BF00500303. [DOI] [PubMed] [Google Scholar]
  8. Ferrell W. R., Russell N. J. Extravasation in the knee induced by antidromic stimulation of articular C fibre afferents of the anaesthetized cat. J Physiol. 1986 Oct;379:407–416. doi: 10.1113/jphysiol.1986.sp016260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Franco-Cereceda A., Rudehill A. Capsaicin-induced vasodilatation of human coronary arteries in vitro is mediated by calcitonin gene-related peptide rather than substance P or neurokinin A. Acta Physiol Scand. 1989 Aug;136(4):575–580. doi: 10.1111/j.1748-1716.1989.tb08704.x. [DOI] [PubMed] [Google Scholar]
  10. Franco-Cereceda A., Rudehill A., Lundberg J. M. Calcitonin gene-related peptide but not substance P mimics capsaicin-induced coronary vasodilation in the pig. Eur J Pharmacol. 1987 Oct 13;142(2):235–243. doi: 10.1016/0014-2999(87)90112-9. [DOI] [PubMed] [Google Scholar]
  11. Gitter B. D., Waters D. C., Bruns R. F., Mason N. R., Nixon J. A., Howbert J. J. Species differences in affinities of non-peptide antagonists for substance P receptors. Eur J Pharmacol. 1991 May 17;197(2-3):237–238. doi: 10.1016/0014-2999(91)90532-u. [DOI] [PubMed] [Google Scholar]
  12. Hornyak M. E., Naver H. K., Rydenhag B., Wallin B. G. Sympathetic activity influences the vascular axon reflex in the skin. Acta Physiol Scand. 1990 May;139(1):77–84. doi: 10.1111/j.1748-1716.1990.tb08899.x. [DOI] [PubMed] [Google Scholar]
  13. Hukkanen M., Grönblad M., Rees R., Kottinen Y. T., Gibson S. J., Hietanen J., Polak J. M., Brewerton D. A. Regional distribution of mast cells and peptide containing nerves in normal and adjuvant arthritic rat synovium. J Rheumatol. 1991 Feb;18(2):177–183. [PubMed] [Google Scholar]
  14. 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. 1975 Dec 19;100(2):235–252. doi: 10.1016/0006-8993(75)90481-3. [DOI] [PubMed] [Google Scholar]
  15. Kangawa K., Minamino N., Fukuda A., Matsuo H. Neuromedin K: a novel mammalian tachykinin identified in porcine spinal cord. Biochem Biophys Res Commun. 1983 Jul 29;114(2):533–540. doi: 10.1016/0006-291x(83)90813-6. [DOI] [PubMed] [Google Scholar]
  16. Lam F. Y., Ferrell W. R. Capsaicin suppresses substance P-induced joint inflammation in the rat. Neurosci Lett. 1989 Oct 23;105(1-2):155–158. doi: 10.1016/0304-3940(89)90028-1. [DOI] [PubMed] [Google Scholar]
  17. Lam F. Y., Ferrell W. R. Inhibition of carrageenan induced inflammation in the rat knee joint by substance P antagonist. Ann Rheum Dis. 1989 Nov;48(11):928–932. doi: 10.1136/ard.48.11.928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lam F. Y., Ferrell W. R. Specific neurokinin receptors mediate plasma extravasation in the rat knee joint. Br J Pharmacol. 1991 May;103(1):1263–1267. doi: 10.1111/j.1476-5381.1991.tb12334.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lee C. M., Iversen L. L., Hanley M. R., Sandberg B. E. The possible existence of multiple receptors for substance P. Naunyn Schmiedebergs Arch Pharmacol. 1982 Mar;318(4):281–287. doi: 10.1007/BF00501166. [DOI] [PubMed] [Google Scholar]
  20. Miller R. C., Stoclet J. C. Modulation by endothelium of contractile responses in rat aorta in absence and presence of flunarizine. Br J Pharmacol. 1985 Nov;86(3):655–661. doi: 10.1111/j.1476-5381.1985.tb08942.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nilsson G. E., Tenland T., Oberg P. A. Evaluation of a laser Doppler flowmeter for measurement of tissue blood flow. IEEE Trans Biomed Eng. 1980 Oct;27(10):597–604. doi: 10.1109/TBME.1980.326582. [DOI] [PubMed] [Google Scholar]
  22. Nilsson G. E., Tenland T., Obert P. A. A new instrument for continuous measurement of tissue blood flow by light beating spectroscopy. IEEE Trans Biomed Eng. 1980 Jan;27(1):12–19. doi: 10.1109/TBME.1980.326686. [DOI] [PubMed] [Google Scholar]
  23. Obeid A. N., Dougherty G., Pettinger S. In vivo comparison of a twin wavelength laser Doppler flowmeter using He-Ne and laser diode sources. J Med Eng Technol. 1990 May-Jun;14(3):102–110. doi: 10.3109/03091909009015421. [DOI] [PubMed] [Google Scholar]
  24. Otsuka M., Konishi S. Substance P and excitatory transmitter of primary sensory neurons. Cold Spring Harb Symp Quant Biol. 1976;40:135–143. doi: 10.1101/sqb.1976.040.01.015. [DOI] [PubMed] [Google Scholar]
  25. Randić M., Miletić V. Effect of substance P in cat dorsal horn neurones activated by noxious stimuli. Brain Res. 1977 Jun 3;128(1):164–169. doi: 10.1016/0006-8993(77)90245-1. [DOI] [PubMed] [Google Scholar]
  26. Regoli D., Drapeau G., Dion S., D'Orléans-Juste P. Pharmacological receptors for substance P and neurokinins. Life Sci. 1987 Jan 12;40(2):109–117. doi: 10.1016/0024-3205(87)90349-3. [DOI] [PubMed] [Google Scholar]
  27. Regoli D., Mizrahi J., D'Orléans-Juste P., Dion S., Drapeau G., Escher E. Substance P antagonists showing some selectivity for different receptor types. Eur J Pharmacol. 1985 Feb 12;109(1):121–125. doi: 10.1016/0014-2999(85)90548-5. [DOI] [PubMed] [Google Scholar]
  28. Snider R. M., Constantine J. W., Lowe J. A., 3rd, Longo K. P., Lebel W. S., Woody H. A., Drozda S. E., Desai M. C., Vinick F. J., Spencer R. W. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science. 1991 Jan 25;251(4992):435–437. doi: 10.1126/science.1703323. [DOI] [PubMed] [Google Scholar]

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