The Effect of Verapamil on the Contractility of Smooth Muscle and on Excitation-Secretion Coupling in Adrenergic Nerve Terminals

Haeusler, G.

doi:10.1159/000157890

Cited by 64 publications

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“…The increase in the frequency of methoxamineand barium-induced responses produced by certain concentrations of verapamil (and also the small increase in frequency of barium response observed with methoxyverapamil) may be caused by membrane depolarization, as reported by Haeusler (1972) for verapamil in similar concentrations in the rabbit main pulmonary artery. An increase in the frequency of 5-HT-induced rhythmic contractions has been reported for verapamil in the identical concentration range (Hay & Wadsworth, 1982b).…”

Section: Discussionmentioning

confidence: 57%

The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug‐induced rhythmic contractions in the rat vas deferens

Hay

Wadsworth

1983

British J Pharmacology

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1 In the rat isolated vas deferens, methoxamine 8.1 gM produced an initial phasic response that declined towards baseline and was followed by rhythmic contractions that continued until wash-out.These responses were predominant in the epididymal half. BaCl2 1 mM produced a similar type of response which was not mediated by noradrenaline release or activation of a-adrenoceptors. The barium responses were similar in the epididymal and prostatic halves.2 Incubation in nominally Ca2'-free solution caused abolition or near abolition of rhythmic contractions produced by barium or methoxamine. The initial phasic response to methoxamine was abolished in Ca2+-free solution, whereas that produced by barium persisted.3 Rhythmic contractions produced by methoxamine or barium were inhibited by Mg2+ (2.4-20mM) and by La3+ (1-5mM). Mg2+ had selectivity for inhibition of the frequency of methoxamine-but not barium-induced rhythmic contractions.4 Despite their dependence on [Ca]2+0, barium-and methoxamine-induced rhythmic contractions were resistant to inhibition by calcium channel inhibitors. Verapamil, nifedipine and flunarazine inhibited the amplitude of rhythmic contractions more readily than the frequency (methoxamine IC50 for verapamil: amplitude=29.8±5.40AM, n =6, frequency=96.7±31.O0AM, n =5, for nifedipine-amplitude = 2.42 ± 0.34 pM, n =7, frequency = 3.24 ± 0.75JAM, n =7, and for flunarizine: amplitude = 15.9 ± 5.95 JAM, n =7, frequency = 153 ± 28.6 JAM, n = 7). There was no differentiation between inhibition of methoxamine and barium-induced responses. 5 Like Mg2+, methoxyverapamil selectively inhibited the frequency of methoxamine-induced contractions (IC50: amplitude = 16.8 ± 2.86 gM, n = 5, frequency -2.07 ± 0.81 JiM, n = 5) but not barium-induced contractions (IC50: amplitude = 13.9 ± 1.95 JAM, n =5, frequency = 48.5 ± 8.98 JAM, n =5).6 Diazoxide (43.3-2 167 JM) and nitroprusside (3.36-6712 MM) had only a small effect on barium contractions, but produced a dose-related reduction in the amplitude of methoxamine-induced responses. Diazoxide and nitroprusside caused methoxamine contractions to occur in groups, although they had no effect on their overall frequency. 7 It is concluded that barium-and methoxamine-induced rhythmic contractions in the rat vas deferens are mediated by the entry of [Ca2+]0 via membrane calcium channels that have a lower affinity (10-100 x) for calcium channel inhibitors than those mediating the KC1 response. Channels activated by methoxamine are concentrated in the epididymal half, whereas those opened by barium are evenly distributed. However, although responses to methoxamine and barium are similar in form, differences in the effects of some of the drugs tested, together with the results of previous studies, indicate that they produce contractions by different mechanisms.

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Section: Discussionmentioning

confidence: 57%

The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug‐induced rhythmic contractions in the rat vas deferens

Hay

Wadsworth

1983

British J Pharmacology

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“…An increase in Ca entry through receptor-operated channels (ROCs) seems to determine the tonic component of NAinduced contractions (Hudgins & Weiss, 1968;Deth & Van Breemen, 1974;Bolton, 1979), whereas both contractile responses induced by high K or by increasing Ca concentration in K-depolarized aortae are thought to be entirely dependent upon the influx of extracellular Ca through voltage-sensitive channels (VSCs) (Hudgins & Weiss, 1968;Godfraind & Kaba, 1969;Bolton, 1979). Propafenone inhibited in a concentration-dependent manner the contractile responses induced by high K depolarization or by Ca which have been used to provide a simple means of studying drugs with possible Ca entry blocking properties (Haeusler, 1972;Godfraind et al, 1986) as well as the tonic component of NAinduced responses. Moreover, in the present experiments propafenone decreased high K-as well as NA-induced contractions which indicated that it may inhibit Ca entry both through VSCs and ROCs.…”

Section: Discussionmentioning

confidence: 99%

Effects of propafenone on ⁴⁵Ca movements and contractile responses in vascular smooth muscle

Carrón

Pérez‐Vizcaíno

Delpón

et al. 1991

British J Pharmacology

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1 In rat isolated aorta the class Ic antiarrhythmic drug, propafenone, dose-dependently inhibited the contractile responses induced by high K (80mM) and noradrenaline (NA, 10-SM), the ICSos being 2.5 + 0.7 x 10-6 M and 8.7 + 0.8 x 10-6 M, respectively. These inhibitory actions were also observed with propafenone added after the induced contractions. 2 Contractile responses induced by addition of Ca to 0 Ca high-K solution were also inhibited by propafenone (IC50 = 2.5 + 0.8 x 10-6M). Moreover, propafenone inhibited the contractile responses elicited by NA in strips incubated in 0 Ca (IC50 = 1.9 + 0.9 X 106M). 3 Propafenone also inhibited (IC50 = 1.2 + 0.4 x 10 -M) the development of spontaneous mechanical activity in portal vein segments.4 Propafenone, 5 x 10-6M and 10-SM, inhibited 45Ca uptake stimulated by high K or NA without altering 45Ca uptake in resting strips. 5 These results indicated that in rat isolated aortae and portal veins propafenone inhibited Ca entry through voltage-operated channels and NA-induced Ca uptake as well as Ca release from intracellular stores. As a consequence it would reduce the concentration of intracellular free Ca available at the contractile apparatus for vascular smooth muscle contraction.

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“…4 and 5) suggests that the initial phase is likely to be evoked by the Ca2+ influx (Golenhofen and Lammel 1972;Haeusler 1972;Mayer et al 1972). An increased membrane conductance at the early phase of NA application may also support this possibility (Fig.…”

Section: Discussionmentioning

confidence: 99%

Possible relationship between the release of calcium ions and inactivation of the potassium conductance induced by noradrenaline in smooth muscle of the Guinea-pig vas deferens.

Wakui

Fukushi

1986

Tohoku J. Exp. Med.

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In order to examine whether any change in cytoplasmic Ca2+ concentration occurs during the noradrenaline (NA)-induced change in the membrane potential, the isometric tension of smooth muscle of the guinea-pig vas deferens was recorded together with membrane potentials using the sucrose-gap method. NA induced a depolarization and an increase in cytoplasmic Ca2+ comprising two (initial and second) phases. In time courses, the depolarization and the second phase of the increase in cytoplasmic Ca2+ were similar. Only at the phase around the onset of the depolarization, the membrane conductance was increased but then, it was decreased. Lowering the external Ca2+ concentration and application of D600 suppressed all of the NA-induced responses. In addition, D600 diminished the size of the NA-induced decrement in the membrane conductance. The present results suggest that the initial phase of the increase in the cytoplasmic Ca2+ is due to the influx of Ca2+ and the second phase, probably to the release of Ca2+ from some intracellular stores. It was discussed that the release of Ca2+ might occur at the internal surface of the membrane, and the membrane might be left less permeable to K+ as a result.noradrenaline ; D600; Ca release ; K inactivation ; guinea-pig vas deferensIn previous reports (Wakui and Inomata 1985; Wakui and Fukushi 1986), we suggested that through a-adrenergic receptor activation, noradrenaline (NA) reduced the K+ conductance and consequently induced the membrane depolarization in smooth muscle of the guinea-pig vas deferens. This hypothesis has been supported by the following evidence in the experiments using the double sucrosegap method : 1) The NA-induced depolarization is associated with a reduction in the membrane conductance. 2) The reversal potential of the NA-induced depolarization is negative to the resting membrane potential. 3) The reversal

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The Effect of Verapamil on the Contractility of Smooth Muscle and on Excitation-Secretion Coupling in Adrenergic Nerve Terminals

Cited by 64 publications

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The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug‐induced rhythmic contractions in the rat vas deferens

The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug‐induced rhythmic contractions in the rat vas deferens

Effects of propafenone on ⁴⁵Ca movements and contractile responses in vascular smooth muscle

Possible relationship between the release of calcium ions and inactivation of the potassium conductance induced by noradrenaline in smooth muscle of the Guinea-pig vas deferens.

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The Effect of Verapamil on the Contractility of Smooth Muscle and on Excitation-Secretion Coupling in Adrenergic Nerve Terminals

Cited by 64 publications

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The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug‐induced rhythmic contractions in the rat vas deferens

The effects of calcium channel inhibitors and other procedures affecting calcium translocation on drug‐induced rhythmic contractions in the rat vas deferens

Effects of propafenone on 45Ca movements and contractile responses in vascular smooth muscle

Possible relationship between the release of calcium ions and inactivation of the potassium conductance induced by noradrenaline in smooth muscle of the Guinea-pig vas deferens.

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Effects of propafenone on ⁴⁵Ca movements and contractile responses in vascular smooth muscle