Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1990 Dec;431:529–541. doi: 10.1113/jphysiol.1990.sp018345

Mechanism of action of substance P in guinea-pig ileum longitudinal smooth muscle: a re-evaluation.

J M Hall 1, I K Morton 1
PMCID: PMC1181789  PMID: 1712846

Abstract

1. A proposed mechanism of contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in membrane K+ permeability (PK) has been re-examined. 2. Potentiation of responses to substance P by the K+ channel blocker tetraethylammonium (TEA) was originally proposed as evidence for a mechanism of action of substance P involving a decrease in PK. Potentiation was confirmed; however this was found not to be specific to substance P since a similar potentiation of responses was seen with agonists not thought to act via a decrease in PK. 3. Antagonism of contractile responses to substance P by noradrenaline was similarly confirmed. However, this antagonism was found to represent a non-specific functional interaction through the inhibitory actions of beta-adrenoceptors rather than the proposed specific interaction with an increase in PK by noradrenaline which is normally alpha 1-adrenoceptor mediated. 4. Experiments were made measuring 86Rb efflux, in depolarized guinea-pig ileum longitudinal smooth muscle, to estimate PK. These studies confirmed a reported decrease in PK with TEA, but failed to detect the previously reported decrease with substance P. 5. These results, although not disproving a suggested mechanism of direct contractile action of substance P in guinea-pig ileum longitudinal smooth muscle involving a decrease in PK, do throw doubt on either the evidence, or its interpretation, as proposed by the original authors in support of such a mechanism.

Full text

PDF
535

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  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. Bailey S. J., Featherstone R. L., Jordan C. C., Morton I. K. An examination of the pharmacology of two substance P antagonists and the evidence for tachykinin receptor subtypes. Br J Pharmacol. 1986 Jan;87(1):79–85. doi: 10.1111/j.1476-5381.1986.tb10159.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bauer V., Kuriyama H. Homogeneous and non-homogeneous distribution of inhibitory and excitatory adrenoceptors in the longitudinal muscle of the guinea-pig ileum. Br J Pharmacol. 1982 Aug;76(4):603–611. doi: 10.1111/j.1476-5381.1982.tb09260.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Benham C. D., Bolton T. B. Comparison of the excitatory actions of substance P, carbachol, histamine and prostaglandin F2 alpha on the smooth muscle of the taenia of the guinea-pig caecum. Br J Pharmacol. 1983 Nov;80(3):409–420. doi: 10.1111/j.1476-5381.1983.tb10710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bolton T. B. Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev. 1979 Jul;59(3):606–718. doi: 10.1152/physrev.1979.59.3.606. [DOI] [PubMed] [Google Scholar]
  6. Bülbring E., Tomita T. Catecholamine action on smooth muscle. Pharmacol Rev. 1987 Mar;39(1):49–96. [PubMed] [Google Scholar]
  7. Bülbring E., Tomita T. Increase of membrane conductance by adrenaline in the smooth muscle of guinea-pig taenia coli. Proc R Soc Lond B Biol Sci. 1969 Mar 11;172(1027):89–102. doi: 10.1098/rspb.1969.0013. [DOI] [PubMed] [Google Scholar]
  8. Bülbring E., Tomita T. Suppression of spontaneous spike generation by catecholamines in the smooth muscle of the guinea-pig taenia coli. Proc R Soc Lond B Biol Sci. 1969 Mar 11;172(1027):103–119. doi: 10.1098/rspb.1969.0014. [DOI] [PubMed] [Google Scholar]
  9. Creed K. E. Functional diversity of smooth muscle. Br Med Bull. 1979 Sep;35(3):243–247. doi: 10.1093/oxfordjournals.bmb.a071584. [DOI] [PubMed] [Google Scholar]
  10. DURBIN R. P., JENKINSON D. H. The effect of carbachol on the permeability of depolarized smooth muscle to inorganic ions. J Physiol. 1961 Jun;157:74–89. doi: 10.1113/jphysiol.1961.sp006706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hanani M., Chorev M., Gilon C., Selinger Z. The actions of receptor-selective substance P analogs on myenteric neurons: an electrophysiological investigation. Eur J Pharmacol. 1988 Aug 24;153(2-3):247–253. doi: 10.1016/0014-2999(88)90612-7. [DOI] [PubMed] [Google Scholar]
  12. Holzer P. An enquiry into the mechanism by which substance P facilitates the phasic longitudinal contractions of the rabbit ileum. J Physiol. 1982 Apr;325:377–392. doi: 10.1113/jphysiol.1982.sp014156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Holzer P., Lippe I. T. Substance P action on phosphoinositides in guinea-pig intestinal muscle: a possible transduction mechanism? Naunyn Schmiedebergs Arch Pharmacol. 1985 Mar;329(1):50–55. doi: 10.1007/BF00695192. [DOI] [PubMed] [Google Scholar]
  14. Holzer P., Lippe I. T. Substance P can contract the longitudinal muscle of the guinea-pig small intestine by releasing intracellular calcium. Br J Pharmacol. 1984 May;82(1):259–267. doi: 10.1111/j.1476-5381.1984.tb16466.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Holzer P., Petsche U. On the mechanism of contraction and desensitization induced by substance P in the intestinal muscle of the guinea-pig. J Physiol. 1983 Sep;342:549–568. doi: 10.1113/jphysiol.1983.sp014868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ito Y., Kuriyama H., Sakamoto Y. Effects of tetraethylammonium chloride on the membrane activity of guinea-pig stomach smooth muscle. J Physiol. 1970 Dec;211(2):445–460. doi: 10.1113/jphysiol.1970.sp009286. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jenkinson D. H., Morton I. K. The effect of noradrenaline on the permeability of depolarized intestinal smooth muscle to inorganic ions. J Physiol. 1967 Feb;188(3):373–386. doi: 10.1113/jphysiol.1967.sp008144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jenkinson D. H., Morton I. K. The role of alpha- and beta- adrenergic receptors in some actions of catecholamines on intestinal smooth muscle. J Physiol. 1967 Feb;188(3):387–402. doi: 10.1113/jphysiol.1967.sp008145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Katayama Y., North R. A. Does substance P mediate slow synaptic excitation within the myenteric plexus? Nature. 1978 Jul 27;274(5669):387–388. doi: 10.1038/274387a0. [DOI] [PubMed] [Google Scholar]
  20. Laufer R., Wormser U., Friedman Z. Y., Gilon C., Chorev M., Selinger Z. Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7444–7448. doi: 10.1073/pnas.82.21.7444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakazawa K., Inoue K., Fujimori K., Takanaka A. Difference between substance P- and acetylcholine-induced currents in mammalian smooth muscle cells. Eur J Pharmacol. 1990 Apr 25;179(3):453–456. doi: 10.1016/0014-2999(90)90188-c. [DOI] [PubMed] [Google Scholar]
  22. RANG H. P. STIMULANT ACTIONS OF VOLATILE ANAESTHETICS ON SMOOTH MUSCLE. Br J Pharmacol Chemother. 1964 Apr;22:356–365. doi: 10.1111/j.1476-5381.1964.tb02040.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sims S. M., Walsh J. V., Jr, Singer J. J. Substance P and acetylcholine both suppress the same K+ current in dissociated smooth muscle cells. Am J Physiol. 1986 Oct;251(4 Pt 1):C580–C587. doi: 10.1152/ajpcell.1986.251.4.C580. [DOI] [PubMed] [Google Scholar]
  24. Souquet J. C., Bitar K. N., Grider J. R., Makhlouf G. M. Receptors for substance P on isolated intestinal smooth muscle cells of the guinea pig. Am J Physiol. 1987 Nov;253(5 Pt 1):G666–G672. doi: 10.1152/ajpgi.1987.253.5.G666. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Watson S. P., Downes C. P. Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus. Eur J Pharmacol. 1983 Sep 30;93(3-4):245–253. doi: 10.1016/0014-2999(83)90144-9. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES