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. 1992 Apr;105(4):925–928. doi: 10.1111/j.1476-5381.1992.tb09079.x

Differences in neurokinin receptor pharmacology between rat and guinea-pig superior cervical ganglia.

G R Seabrook 1, M Main 1, B Bowery 1, N Wood 1, R G Hill 1
PMCID: PMC1908729  PMID: 1380375

Abstract

1. The depolarizations elicited by seven neurokinin receptor agonists were examined in both rat and guinea-pig superior cervical ganglia by use of grease-gap methodology in the presence of tetrodotoxin (0.1 microM). Responses were normalised with respect to 1 microM eledoisin. 2. The rank order of agonist potency in the rat ganglia was senktide greater than substance P greater than substance P methyl ester = eleidosin = Sar-Met-substance P greater than neurokinin B greater than neurokinin A, whereas in guinea-pig superior cervical ganglion (SCG) the rank order was senktide greater than Sar-Met-substance P greater than neurokinin B = eledoisin = substance P methyl ester. The concentration-effect curves for substance P and neurokinin A in guinea-pig ganglia were biphasic which precluded the determination of meaningful potency values. 3. The maximal depolarization achieved by subtype selective ligands was different between these two species. On rat and guinea-pig SCG, the NK3-selective ligand, senktide, produced a maximal depolarization of 27% and 274% respectively, whereas the NK1-selective ligand, substance P methyl ester, produced depolarizations of 77% and 64% respectively. 4. The depolarizations induced by substance P methyl ester and senktide in either species were unaffected by atropine (1 microM), suggesting a lack of involvement of presynaptic neurokinin receptors in the generation of the response. 5. The potency of substance P methyl ester, senktide, and neurokinin A were unaffected by pretreating ganglia with the peptidase inhibitors bacitracin (40 micrograms ml-1), leupeptin (4 micrograms ml-1), and chymostatin (2 micrograms ml-1). Similarly, these peptidase inhibitors had no effect on the maximal depolarizations achieved by any of these agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. Adams P. R., Brown D. A., Jones S. W. Substance P inhibits the M-current in bullfrog sympathetic neurones. Br J Pharmacol. 1983 Jun;79(2):330–333. doi: 10.1111/j.1476-5381.1983.tb11004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown D. A., Fatherazi S., Garthwaite J., White R. D. Muscarinic receptors in rat sympathetic ganglia. Br J Pharmacol. 1980 Dec;70(4):577–592. doi: 10.1111/j.1476-5381.1980.tb09777.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chang M. M., Leeman S. E. Isolation of a sialogogic peptide from bovine hypothalamic tissue and its characterization as substance P. J Biol Chem. 1970 Sep 25;245(18):4784–4790. [PubMed] [Google Scholar]
  4. Creutzfeldt W., Ebert R., Finke U., Konturek S. J., Kwiecień N., Radecki T. Inhibition of gastric secretion by fat and hypertonic glucose in the dog: role of gastric inhibitory peptide. J Physiol. 1983 Jan;334:91–101. doi: 10.1113/jphysiol.1983.sp014482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dalsgaard C. J., Hökfelt T., Elfvin L. G., Skirboll L., Emson P. Substance P-containing primary sensory neurons projecting to the inferior mesenteric ganglion: evidence from combined retrograde tracing and immunohistochemistry. Neuroscience. 1982 Mar;7(3):647–654. doi: 10.1016/0306-4522(82)90070-7. [DOI] [PubMed] [Google Scholar]
  6. Dun N. J., Karczmar A. G. Actions of substance P on sympathetic neurons. Neuropharmacology. 1979 Feb;18(2):215–218. doi: 10.1016/0028-3908(79)90064-9. [DOI] [PubMed] [Google Scholar]
  7. Guard S., Watson S. P., Maggio J. E., Too H. P., Watling K. J. Pharmacological analysis of [3H]-senktide binding to NK3 tachykinin receptors in guinea-pig ileum longitudinal muscle-myenteric plexus and cerebral cortex membranes. Br J Pharmacol. 1990 Apr;99(4):767–773. doi: 10.1111/j.1476-5381.1990.tb13004.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guyenet P. G., Aghajanian G. K. Excitation of neurons in the nucleus locus coeruleus by substance P and related peptides. Brain Res. 1977 Nov 4;136(1):178–184. doi: 10.1016/0006-8993(77)90144-5. [DOI] [PubMed] [Google Scholar]
  9. Hawcock A. B., Hayes A. G., Tyers M. B. Agonist effects of [D-Pro2,D-Phe7,D-Trp9]substance P--evidence for different receptors. Eur J Pharmacol. 1982 May 7;80(1):135–138. doi: 10.1016/0014-2999(82)90189-3. [DOI] [PubMed] [Google Scholar]
  10. Hökfelt T., Elfvin L. G., Schultzberg M., Goldstein M., Nilsson G. On the occurrence of substance P-containing fibers in sympathetic ganglia: immunohistochemical evidence. Brain Res. 1977 Aug 19;132(1):29–41. doi: 10.1016/0006-8993(77)90704-1. [DOI] [PubMed] [Google Scholar]
  11. Ireland S. J., Bailey F., Cook A., Hagan R. M., Jordan C. C., Stephens-Smith M. L. Receptors mediating tachykinin-induced contractile responses in guinea-pig trachea. Br J Pharmacol. 1991 Jun;103(2):1463–1469. doi: 10.1111/j.1476-5381.1991.tb09812.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Nakajima Y., Nakajima S., Inoue M. Pertussis toxin-insensitive G protein mediates substance P-induced inhibition of potassium channels in brain neurons. Proc Natl Acad Sci U S A. 1988 May;85(10):3643–3647. doi: 10.1073/pnas.85.10.3643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Newberry N. R., Cheshire S. H., Gilbert M. J. Evidence that the 5-HT3 receptors of the rat, mouse and guinea-pig superior cervical ganglion may be different. Br J Pharmacol. 1991 Mar;102(3):615–620. doi: 10.1111/j.1476-5381.1991.tb12221.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nowak L. M., Macdonald R. L. Substance P: ionic basis for depolarizing responses of mouse spinal cord neurons in cell culture. J Neurosci. 1982 Aug;2(8):1119–1128. doi: 10.1523/JNEUROSCI.02-08-01119.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Renzetti A. R., Barsacchi P., Criscuoli M., Lucacchini A. Characterization of NK-3 binding sites in rat and guinea pig cortical membranes by the selective ligand [3H]Senktide. Neuropeptides. 1991 Mar;18(3):107–114. doi: 10.1016/0143-4179(91)90101-n. [DOI] [PubMed] [Google Scholar]
  17. Robinson S. E., Schwartz J. P., Costa E. Substance P in the superior cervical ganglion and the submaxillary gland of the rat. Brain Res. 1980 Jan 20;182(1):11–17. doi: 10.1016/0006-8993(80)90826-4. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Stanfield P. R., Nakajima Y., Yamaguchi K. Substance P raises neuronal membrane excitability by reducing inward rectification. Nature. 1985 Jun 6;315(6019):498–501. doi: 10.1038/315498a0. [DOI] [PubMed] [Google Scholar]
  20. V Euler U. S., Gaddum J. H. An unidentified depressor substance in certain tissue extracts. J Physiol. 1931 Jun 6;72(1):74–87. doi: 10.1113/jphysiol.1931.sp002763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ward P., Ewan G. B., Jordan C. C., Ireland S. J., Hagan R. M., Brown J. R. Potent and highly selective neurokinin antagonists. J Med Chem. 1990 Jul;33(7):1848–1851. doi: 10.1021/jm00169a003. [DOI] [PubMed] [Google Scholar]
  22. Wormser U., Laufer R., Hart Y., Chorev M., Gilon C., Selinger Z. Highly selective agonists for substance P receptor subtypes. EMBO J. 1986 Nov;5(11):2805–2808. doi: 10.1002/j.1460-2075.1986.tb04571.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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