Advertisement

Electrical and Mechanical Responses of Vascular Muscle to Tachykinins

  • G. Haeusler
  • J.-E. de Peyer
Conference paper

Summary

Neurokinin A, eledoisin and substance P contracted strips of rabbit main pulmonary artery in a concentration-dependent manner with neurokinin A and eledoisin being 300fold more potent than substance P. Substance P methyl ester was inactive. Neurokinin A and substance P relaxed precontracted vascular strips provided that the endothelium was intact. The rank order of potency of the various agonists suggested the existence of a muscular SP-E type and possibly an endothelial SP-P type tachykinin receptor for the rabbit main pulmonary artery. Porcine coronary artery was devoid of excitatory muscular tachykinin receptors but contained an endothelial SP-P type receptor which, similar to that in the rabbit main pulmonary artery, mediated vasorelaxation. Stimulation of the muscular tachykinin receptor in the rabbit main pulmonary artery resulted in depolarization of the membrane of the smooth muscle cells. In the porcine coronary artery, activation of the endothelial tachykinin receptor produced hyperpolarization of the smooth muscle membrane in all probability through release of endothelium derived relaxing factor. Neurokinin A- and substance P-induced contractions of rabbit main pulmonary artery were not susceptible to inhibition by calcium antagonists and were not affected by pertussis toxin-induced inactivation of a guanine nucleotide binding regulatory protein (N.). It is, therefore, suggested that activation of the smooth muscle tachykinin receptor leads predominantly to a release of calcium from the sarcoplasmic reticulum and that N. is not involved in signal transductioft between the tachykinin receptor and the subsequent steps initiating contraction.

Keywords

Sarcoplasmic Reticulum Porcine Coronary Artery Tachykinin Receptor Tetraethylammonium Chloride Smooth Muscle Membrane 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    D’Orleans-Juste P, Dion S, Drapeau G, Regoli D (1986) Different receptors are involved in the endotheliummediated relaxation and the smooth muscle contraction of the rabbit pulmonary artery in response to substance P and related neurokinins. European J Pharmacol 125:37–44CrossRefGoogle Scholar
  2. 2.
    Gulati N, Beny JL, Mathison R, Regoli D, Huggel H (1986) Pharmacological characterization of tachykinin receptors on the endothelium of isolated pig coronary artery. Experientia (in press)Google Scholar
  3. 3.
    Haeusler G (1978) Relationship between noradrenaline-induced depolarization and contraction in vascular smooth muscle. Blood Vessels 15:46–54PubMedGoogle Scholar
  4. 4.
    Haeusler G, Thorens S (1980) Effects of tetraethylammonium chloride on contractile, membrane and cable properties of rabbit artery muscle. J Physiol (Lond) 303:203–224Google Scholar
  5. 5.
    Watson SP, Sandberg BEB, Hanley MR, Iversen LL (1983) Tissue selectivity of substance P alkyl esters suggesting mUltiple receptors. European J Pharmacol 87:77–84CrossRefGoogle Scholar
  6. 6.
    Laufer R, Wormser U, Friedmann ZY, Gilon C, Chorev M, Selinger Z (1985) Neurokinin B is a preferred agonist for a neuronal substance P receptor and its action is antagonized by enkephalin. Proc Natl Acad Sci USA 82: 7444–7448PubMedCrossRefGoogle Scholar
  7. 7.
    Haeusler G (1983) Contraction, membrane potential, and calcium fluxes in rabbit pulmonary arterial muscle. Fed Proc 42:263–268PubMedGoogle Scholar
  8. 8.
    Haeusler G (1984) Vascular smooth muscle and drugs affecting calcium channels. In: Paton W, Mitchell J, Turner P (eds) Proceedings of the IUPHAR 9th international congress of pharmacology, vol 2. London: Macmillan PressGoogle Scholar
  9. 9.
    Haeusler G, de Peyer J, Yajima M (1985) Characterization of vasoconstriction in response to alPhad- and alpha 2-agonists. Naunyn-Schmie eberg’s Arch Pharmacol 329:R 78Google Scholar
  10. 10.
    Watson SP, Downes CP (1983) Substance P induced hydrolysis of inositol phospholipids in guinea-pig ileum and rat hypothalamus. European J Pharmacol 93:245–253CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1987

Authors and Affiliations

  • G. Haeusler
    • 1
  • J.-E. de Peyer
    • 1
  1. 1.Pharmaceutical Research DepartmentE. MerckDarmstadtGermany

Personalised recommendations