Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 Jan;108(1):132–138. doi: 10.1111/j.1476-5381.1993.tb13452.x

Mediation by the same muscarinic receptor subtype of phasic and tonic contractile activities in the rat isolated portal vein.

M Pfaffendorf 1, P A Van Zwieten 1
PMCID: PMC1907722  PMID: 8428203

Abstract

1. The effects of several agonists on the phasic and tonic contractile responses to muscarinic receptor stimulation have been investigated in the rat portal vein in vitro. 2. Neither chemical denervation with 6-hydroxydopamine nor the presence of the alpha 1-adrenoceptor antagonist, prazosin, influenced the spontaneous or the stimulated myogenic activity of the portal vein. 3. Indomethacin and NG-nitro-L-arginine were used to investigate the influence of vasoactive factors in this preparation. They slightly increased the frequency and the amplitude of the spontaneous myogenic activity of the portal vein, respectively. NG-nitro-L-arginine but not indomethacin enhanced the maximal phasic response to carbachol. Both indomethacin and NG-nitro-L-arginine failed to influence the tonic response to carbachol. 4. Muscarinic agonists increased phasic activity according to the rank order of potency: acetylcholine > muscarine > methacholine > carbachol > aceclidine > bethanechol. These effects were superimposed on a sustained contracture at higher concentrations. Oxotremorine was more potent than arecoline in increasing the mechanical phasic activity, without inducing a sustained contracture. Pilocarpine and McN A343 were weak agonists, producing submaximal effects only on phasic activity. 5. The muscarinic antagonists AF-DX116, 4-diphenylacetoxy-N-methylpiperidine (4-DAMP), P-fluorohexahydrosiladiphenidol (pFHHSiD) and pirenzepine antagonized the phasic and tonic mechanical responses to carbachol. Although the tonic contracture was slightly more sensitive to all antagonists studied, the rank order of potency: 4-DAMP > pFHHSiD > pirenzepine > AF-DX 116 was the same for both types of responses, which is indicative of a M3-receptor subtype.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
132

Selected References

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

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aprigliano O., Hermsmeyer K. In vitro denervation of the portal vein and caudal artery of the rat. J Pharmacol Exp Ther. 1976 Sep;198(3):568–577. [PubMed] [Google Scholar]
  3. Blair-West J. R., McKenzie J. S., McKinley M. J. The actions of angiotensin II on the isolated portal vein of the rat. Eur J Pharmacol. 1971 Jul;15(2):221–230. doi: 10.1016/0014-2999(71)90177-4. [DOI] [PubMed] [Google Scholar]
  4. Brown J. H., Goldstein D. Differences in muscarinic receptor reserve for inhibition of adenylate cyclase and stimulation of phosphoinositide hydrolysis in chick heart cells. Mol Pharmacol. 1986 Dec;30(6):566–570. [PubMed] [Google Scholar]
  5. Burgen A. S., Hiley C. R., Young J. M. The binding of (3H)-propylbenzilycholine mustard by longitudinal muscle strips from guinea-pig small intestine. Br J Pharmacol. 1974 Jan;50(1):145–151. doi: 10.1111/j.1476-5381.1974.tb09602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. De Mey J. G., Vanhoutte P. M. Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium. Circ Res. 1982 Oct;51(4):439–447. doi: 10.1161/01.res.51.4.439. [DOI] [PubMed] [Google Scholar]
  7. Doods H. N., Mathy M. J., Davidesko D., van Charldorp K. J., de Jonge A., van Zwieten P. A. Selectivity of muscarinic antagonists in radioligand and in vivo experiments for the putative M1, M2 and M3 receptors. J Pharmacol Exp Ther. 1987 Jul;242(1):257–262. [PubMed] [Google Scholar]
  8. Duckles S. P. Vascular muscarinic receptors: pharmacological characterization in the bovine coronary artery. J Pharmacol Exp Ther. 1988 Sep;246(3):929–934. [PubMed] [Google Scholar]
  9. Eglen R. M., Michel A. D., Montgomery W. W., Kunysz E. A., Machado C. A., Whiting R. L. The interaction of parafluorohexahydrosiladiphenidol at muscarinic receptors in vitro. Br J Pharmacol. 1990 Apr;99(4):637–642. doi: 10.1111/j.1476-5381.1990.tb12983.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Eglen R. M., Montgomery W. W., Whiting R. L. Negative and positive inotropic responses to muscarinic agonists in guinea pig and rat atria in vitro. J Pharmacol Exp Ther. 1988 Dec;247(3):911–917. [PubMed] [Google Scholar]
  11. FUNAKI S., BOHR D. F. ELECTRICAL AND MECHANICAL ACTIVITY OF ISOLATED VASCULAR SMOOTH MUSCLE OF THE RAT. Nature. 1964 Jul 11;203:192–194. doi: 10.1038/203192b0. [DOI] [PubMed] [Google Scholar]
  12. Furchgott R. F., Vanhoutte P. M. Endothelium-derived relaxing and contracting factors. FASEB J. 1989 Jul;3(9):2007–2018. [PubMed] [Google Scholar]
  13. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  14. Garcia-Villalon A. L., Krause D. N., Ehlert F. J., Duckles S. P. Heterogeneity of muscarinic receptor subtypes in cerebral blood vessels. J Pharmacol Exp Ther. 1991 Jul 1;258(1):304–310. [PubMed] [Google Scholar]
  15. Giachetti A., Micheletti R., Montagna E. Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist. Life Sci. 1986 May 5;38(18):1663–1672. doi: 10.1016/0024-3205(86)90410-8. [DOI] [PubMed] [Google Scholar]
  16. Imai S., Ohta H. Positive inotropic effects induced by carbachol in rat atria treated with islet-activating protein (IAP)--association with phosphatidylinositol breakdown. Br J Pharmacol. 1988 Jun;94(2):347–354. doi: 10.1111/j.1476-5381.1988.tb11536.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jaiswal N., Malik K. U. Prostacyclin synthesis elicited by cholinergic agonists is linked to activation of M2 alpha and M2 beta muscarinic receptors in the rabbit aorta. Prostaglandins. 1990 Mar;39(3):267–280. doi: 10.1016/0090-6980(90)90046-x. [DOI] [PubMed] [Google Scholar]
  18. Kato T., Iwama Y., Okumura K., Hashimoto H., Ito T., Satake T. Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. Hypertension. 1990 May;15(5):475–481. doi: 10.1161/01.hyp.15.5.475. [DOI] [PubMed] [Google Scholar]
  19. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  20. Kenakin T. Drugs and receptors. An overview of the current state of knowledge. Drugs. 1990 Nov;40(5):666–687. doi: 10.2165/00003495-199040050-00003. [DOI] [PubMed] [Google Scholar]
  21. Lambrecht G., Feifel R., Wagner-Röder M., Strohmann C., Zilch H., Tacke R., Waelbroeck M., Christophe J., Boddeke H., Mutschler E. Affinity profiles of hexahydro-sila-difenidol analogues at muscarinic receptor subtypes. Eur J Pharmacol. 1989 Sep 1;168(1):71–80. doi: 10.1016/0014-2999(89)90634-1. [DOI] [PubMed] [Google Scholar]
  22. Leff P., Dougall I. G., Harper D. H., Dainty I. A. Errors in agonist affinity estimation: do they and should they occur in isolated tissue experiments? Trends Pharmacol Sci. 1990 Feb;11(2):64–67. doi: 10.1016/0165-6147(90)90319-4. [DOI] [PubMed] [Google Scholar]
  23. Mülsch A., Busse R. NG-nitro-L-arginine (N5-[imino(nitroamino)methyl]-L-ornithine) impairs endothelium-dependent dilations by inhibiting cytosolic nitric oxide synthesis from L-arginine. Naunyn Schmiedebergs Arch Pharmacol. 1990 Jan-Feb;341(1-2):143–147. doi: 10.1007/BF00195071. [DOI] [PubMed] [Google Scholar]
  24. O'Rourke S. T., Vanhoutte P. M. Subtypes of muscarinic receptors on adrenergic nerves and vascular smooth muscle of the canine saphenous vein. J Pharmacol Exp Ther. 1987 Apr;241(1):64–67. [PubMed] [Google Scholar]
  25. Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
  26. Palmer R. M., Rees D. D., Ashton D. S., Moncada S. L-arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem Biophys Res Commun. 1988 Jun 30;153(3):1251–1256. doi: 10.1016/s0006-291x(88)81362-7. [DOI] [PubMed] [Google Scholar]
  27. Ringdahl B. Determination of dissociation constants and relative efficacies of oxotremorine analogs at muscarinic receptors in the guinea-pig ileum by pharmacological procedures. J Pharmacol Exp Ther. 1984 Apr;229(1):199–206. [PubMed] [Google Scholar]
  28. Uematsu T., Takiguchi Y., Nakashima M. Extrinsic innervation of the canine superior vena cava, pulmonary, portal and renal veins. Angiology. 1984 Aug;35(8):486–493. doi: 10.1177/000331978403500803. [DOI] [PubMed] [Google Scholar]
  29. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]
  30. Van Charldorp K. J., Davidesko D., Van Zwieten P. A. Selectivity of methoctramine for muscarinic receptors in porcine cerebral arteries. Eur J Pharmacol. 1988 May 20;150(1-2):197–199. doi: 10.1016/0014-2999(88)90770-4. [DOI] [PubMed] [Google Scholar]
  31. Watson M., Yamamura H. I., Roeske W. R. [3H]pirenzepine and (-)-[3H]quinuclidinyl benzilate binding to rat cerebral cortical and cardiac muscarinic cholinergic sites. I. Characterization and regulation of agonist binding to putative muscarinic subtypes. J Pharmacol Exp Ther. 1986 May;237(2):411–418. [PubMed] [Google Scholar]
  32. Yoshioka K., Furuta T., Hayakawa A., Ishikawa N., Shigei T. Excitatory cholinergic innervation in canine portal and mesenteric veins. Am J Physiol. 1988 Aug;255(2 Pt 2):H288–H294. doi: 10.1152/ajpheart.1988.255.2.H288. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES