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Calcium-antagonistic effects on the spontaneous activity of guinea-pig taenia coli

Summary

Iproveratril suppresses the amplitude of spontaneous and K-induced phasic contractions of isolated preparations of guinea-pig taenia coli. The dose-response curves obtained in Krebs solution with different Ca concentrations reveal a competitive antagonism between Ca and iproveratril. One molecule of iproveratril is able to antagonize about 8000 Ca ions.

Intracellular measurements of electrical activity, recorded simultaneously with tension, indicate that the drug decreases contractile force primarily by reducing the frequency of action potentials. In addition, a slight impairment of electro-mechanical coupling may contribute to a further reduction of tension. Iproveratril suppresses the rate of rise and fall and the overshoot of the action potential and slows down the pacemaker potential preceding and initating the spike. These inhibiting effects are antagonized by increasing the extracellular Ca concentration. The membrane potential and its slow fluctuations (minute rhythm) appear to be rather resistant to the drug.

These findings indicate that iproveratril suppresses the rate of spike discharges by impairing the mechanisms underlying the spike formation and the pacemaker potential. The results are consistent with the hypothesis that the spike may be carried by an inward current of Ca ions and support the concept that Ca is essential for pacemaker mechanism.

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References

  • Brading, A. F., Bülbring, E., Tomita, T.: The effect of sodium and calcium on the action potential of the smooth muscle of the guinea-pig taenia coli. J. Physiol. (Lond.)200, 637–654 (1969)

    Google Scholar 

  • Bülbring, E.: Correlation between membrane potential, spike discharge and tension in smooth muscle. J. Physiol. (Lond.)128, 200–221 (1955)

    Google Scholar 

  • Edman, K. A. P., Schild, H. O.: The need for calcium in the contractile responses induced by acetylcholine and potassium in the rat uterus. J. Physiol. (Lond.)161, 424–441 (1962)

    Google Scholar 

  • Fleckenstein, A., Gruen, G., Tritthart, H., Byon, K.: Uterus-Relaxation durch hochaktive Ca++-antagonistische Hemmstoffe der elektromechanischen Koppelung wie Isoptin (Verapamil, Iproveratril), Substanz D 600 und Segontin (Prenylamin). Klin. Wschr.49, 32–41 (1971)

    Google Scholar 

  • Fleckenstein, A., Tritthart, H., Döring, H.-J., Byon, K.: Bay a 1040-ein hochaktiver Ca++-antagonistischer Inhibitor der elektromechanischen Koppelungsprozesse im Warmblüter-Myokard. Arzneimittel-Forsch. (Drug Res.)22, 22–33 (1972)

    Google Scholar 

  • Fleckenstein, A., Tritthart, H., Fleckenstein, B., Herbst, A., Gruen, G.: Selektive Hemmung der Myokard-Contractilität durch kompetitive Ca++-Antagonisten (Iproveratril, D 600, Prenylamin). Naunyn-Schmiedebergs Arch. Pharmak.264, 227–228 (1969)

    Google Scholar 

  • Golenhofen, K.: Slow rhythms in smooth muscle (minute-rhythm). In: E. Bülbring et al. (Ed): Smooth muscle, pp. 316–342. London: Ed. Arnold Ltd. 1970

    Google Scholar 

  • Golenhofen, K., Lammel, E.: Selective suppression of some components of spontaneous activity in various types of smooth muscle by Iproveratril (Verapamil). Pflügers Arch.331, 233–243 (1972)

    Google Scholar 

  • Golenhofen, K., Loh, D. v.: Elektrophysiologische Untersuchungen zur normalen Spontanaktivität der isolierten Taenia coli des Meerschweinchens. Pflügers Arch.314, 312–328 (1970)

    Google Scholar 

  • Gruen, G., Fleckenstein, A.: Die elektromechanische Entkoppelung der glatten Gefäßmuskulatur als Grundprinzip der Koronardilatation durch 4-(2′-Nitrophenyl)-2,6-dimethyl-1,4-dihydropyridin-3,5-dicarbonsäure-dimentylester (BAY a 1040, Nifedipine). Arzneimittel-Forsch. (Drug. Res.)22, 334–344 (1972)

    Google Scholar 

  • Gruen, G., Fleckenstein, A., Tritthart, H.: Elektromechanische Entkoppelung durch “muskulotrope” Relaxantien an der Unterusmuskulatur. Naunyn-Schmiedebergs Arch. Pharmak.264, 239–240 (1969)

    Google Scholar 

  • Haas, H., Haertfelder, G.: (α-isopropyl-α-[(N-methyl-N-homoveratryl)-γ-aminopropyl]-3,4-dimethoxyphenylacetonitril-hydrochlorid)1, eine Substanz mit coronargefäßerweiternden Eigenschaften. Arzneimittel-Forsch. (Drug Res.)12, 549–558 (1962)

    Google Scholar 

  • Haeusler, G.: Differential effect of verapamil on excitation-contraction coupling in smooth muscle and on excitation-secretion coupling in adrenergic nerve terminals. J. Pharmacol. exp. Ther.180, 672–682 (1972)

    Google Scholar 

  • Hodgkin, A. L., Huxley, A. F.: A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. (Lond.)117, 500–544 (1952)

    Google Scholar 

  • Imai, S., Takeda, K.: Action of calcium and certain multivalent cations on potassium contracture of guinea-pig's taenia coli. J. Physiol. (Lond.)190, 155–169 (1967)

    Google Scholar 

  • Janke, J., Jaedicke, W., Fleckenstein, A.: Verhinderung isoproterenol-induzierter Myokard-Nekrosen durch Hemmung des transmembranären Ca++-Influx mittels K+-und Mg++-Salzen bzw. Ca++-antagonistischen Hemmstoffen der elektromechanischen Koppelung. Pflügers Arch.319, R8 (1970)

    Google Scholar 

  • Kohlhardt, M., Bauer, B., Krause, H., Fleckenstein, A.: Differentiation of the transmembrane Na and Ca channels in mammalian cardiac fibres by the use of specific inhibitors. Pflügers Arch.335, 309–322 (1972)

    Google Scholar 

  • Kosche, F., Raff, K. W., Lochner, W.: Über die Beeinflussung der Wirkung von Coronardilatatoren durch die extracelluläre Calciumkonzentration (ein Beitrag zum Wirkungsmechanismus von Coronardilatatoren). Pflügers Arch.335, 46–57 (1972)

    Google Scholar 

  • Kuriyama, H.: Effects ions and drugs on the electrical activity of smooth muscle. In: E. Bülbring et al. (Ed.): Smooth muscle, pp. 366–395. London: Ed. Arnold Ltd. 1970

    Google Scholar 

  • Lineweaver, H., Burk, D.: The determination of enzyme dissociation constants, J. Amer. chem. Soc.56, 658–666 (1934)

    Google Scholar 

  • Mayer, C. J., van Breemen, C., Casteels, R.: The action of Lanthanum and D 600 on the calcium exchange in the smooth muscle cells of the guinea-pig taenia coli. Pflügers Arch.337, 333–350 (1972)

    Google Scholar 

  • Peiper, U., Griebel, L., Wende, W.: Activation of vascular smooth muscle of rat aorta by noradrenaline and depolarisation: two different mechanisms. Pflügers Arch.330, 74–89 (1971)

    Google Scholar 

  • Peiper, U., Schmidt, E.: Relaxation of coronary arteries by electro-mechanical decoupling or adrenergic stimulation. Pflügers Arch.337, 107–117 (1972)

    Google Scholar 

  • Riemer, J., Mayer, C. J., Ulbrecht, G.: Der Temperatureinfluß auf die spontane elektrische Aktivität der Taenia coli des Meerschweinchens. Pflügers Arch.319, R120 (1970)

    Google Scholar 

  • Riemer, J., Mayer, C. J., Ulbrecht, G.: Determination of membrane potential in smooth muscle cells using microelectrodes with reduced tip potential. Pflügers Arch.349, 267–275 (1974)

    Google Scholar 

  • Tomita, t.: Electrical properties of mammalian smooth muscle. In: E. Bülbring et al. (Ed.): Smooth muscle, pp. 197–243. London: Ed. Arnold Ltd. 1970

    Google Scholar 

  • Tomita, T.: Spike propagation in the smooth muscle of the guinea-pig taenia coli. J. Physiol. (Lond.)191, 517–527 (1967)

    Google Scholar 

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Supported by the Deutsche Forschungsgemeinschaft (Ul 8/5)

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Riemer, J., Dörfler, F., Mayer, CJ. et al. Calcium-antagonistic effects on the spontaneous activity of guinea-pig taenia coli. Pflugers Arch. 351, 241–258 (1974). https://doi.org/10.1007/BF00586921

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  • DOI: https://doi.org/10.1007/BF00586921

Key words

  • Smooth Muscle
  • Electro-Mechanical Coupling
  • Iproveratril
  • Action Potential
  • Pacemaker Potential
  • Ca Ions