Effects of Verapamil on [3H]Norepinephrine Release

Zsoter, T; Wolchinsky, C.; Endrényi, László

doi:10.1097/00005344-198406060-00011

Cited by 15 publications

(6 citation statements)

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“…8 To facilitate the observation of thermogenic effects of benidipine, we ®rst examined the effect of benidipine in cold-acclimated rats which have a large thermogenic capacity, due to their recruited BAT. 9 As seen in the exempli®ed experiment in Figure 3A, in the metabolic chamber with an ambient temperature of 28 C, the rat examined here initially had a . An injection of NA -at a dose earlier established 13 to yield a maximal thermogenic response from BAT -led, as expected, to a large (2 ± 3-fold) increase in oxygen consumption (thermogenesis) ( Figure 3A).…”

Section: Thermogenic Effect Of Benidipine In Vivomentioning

confidence: 99%

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

et al. 1999

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BACKGROUND: Anti-obesity effects of calcium antagonists such as benidipine and nifedipine have been described in rodent obesity models, but the mode of action of the calcium antagonists as anti-obesity agents has not been established. OBJECTIVE: To examine whether the anti-obesity effects of calcium antagonists (here benidipine) could be ascribed to a direct stimulation of brown adipose tissue (BAT) thermogenesis. METHODS: Examination of the ability of benidipine to induce thermogenesis (increased rate of oxygen consumption) in isolated brown-fat cells from rats, mice and hamsters -and in intact cold-acclimated rats. RESULTS: Benidipine itself, or in combination with any dose of noradrenaline (NA), was totally unable to induce or augment thermogenesis in isolated brown-fat cells of any species tested. However, it markedly induced thermogenesis in intact animals (approx 60% increase over resting metabolic rate). This effect could be fully inhibited by propranolol. CONCLUSION: Benidipine is itself without thermogenic effect. The thermogenic response in-vivo (and thus presumably the anti-obesity effect) is probably secondary to a previously described general side-effect of calcium antagonists: a release of NA from sympathetic nerves, here most likely directly from nerves in the BAT. The antiobesity effect of benedipine is thus probably not due to its calcium channel blocking effect. PERSPECTIVES: It is probable that the anti-obesity effects of calcium antagonists reported in several models of genetically obese rodents (MSG-obese and agouti mice, SHHFaMcc-fa cp and JCR:LA-corpulent rats) are mediated via an indirect stimulation of BAT. To what extent calcium antagonists may induce similar effects in a clinical situation, is currently unknown.

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Section: Thermogenic Effect Of Benidipine In Vivomentioning

confidence: 99%

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

et al. 1999

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“…The release of noradrenaline in this organ has been previously shown to be insensitive to blockade by verapamil (Zsoter et al, 1984) or diltiazem (Hicks et al, 1985).…”

Section: Introductionmentioning

confidence: 98%

Inhibition of noradrenaline release by ω‐conotoxin GVIA in the rat tail artery

Clasbrummel

Oßwald²,

Illéš

1989

British J Pharmacology

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1 The perivascular nerves of isolated tail arteries from Wistar rats were stimulated with field pulses (1 Hz, 2 pulses, every 2 min). w-Conotoxin 1Onmol depressed neurogenically mediated contractions, but did not influence the contractions to noradrenaline 0.1-0.3 pmol -1.2 The inhibitory effect of cw-conotoxin was concentration-dependent (IC50 = 3.8nmollP). It did not reach a steady-state during 30min incubation and could not be reversed upon subsequent washout for another 60 min. 3 A gradual increase in the Ca2 + concentration of the medium from 1.25 mmol I -' to 10 mmol I1 enhanced vasoconstriction and attenuated the action of w-conotoxin 10nmoll-'. When a low stimulation intensity (120mA) was used at high external Ca2+ (10 mmollP1), similar contractile responses were obtained as under normal conditions (200mA current, 2.5mmoll-' Ca2 ). However, the inverse relationship between the effect of the toxin and external Ca2+ remained unchanged. 4 The time-course and degree of the inhibition by co-conotoxin 3nmollP1 was identical in tail arteries of spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). 5 When tail arteries of Wistar rats were preincubated with [3H]-noradrenaline, field stimulation (0.4 Hz, 24 pulses, every 16 min) evoked tritium overflow and vasoconstriction. cw-Conotoxin 30 nmol I -1 inhibited both responses to a similar extent.6 Our results suggest that (o-conotoxin selectively blocks Ca2 + channels in the terminals of perivascular nerves and thereby reduces the release, but not the contractile effect of the sympathetic transmitter.

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“…The pivotal role of Ca2+ in promoting transmitter release from adrenergic nerve terminals during depolarization has been well established (see reviews by Katz, 1969;Llinis & Heuser, 1977). The demonstration that high doses of (Zsoter et al, 1984;Wolchinsky & Zsoter, 1985). These observations together with the finding that high-affinity binding of [3H]-nitrendipine is directly linked to inhibition of voltage-dependent Ca2 + uptake in smooth muscle (Bolger et al, 1983), but not in rat cortical synaptosomes (Wei & Chiang, 1985), suggest that Ca2 + channels at adrenergic nerve terminal probably differ in various tissues and species and are also distinct from those located in cardiac and smooth muscle.…”

Section: Introductionmentioning

confidence: 99%

Differential effect of ω‐conotoxin on release of the adrenergic transmitter and the vasoconstrictor response to noradrenaline in the rat isolated kidney

El-Din

Malik

1988

British J Pharmacology

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(6pM) failed to alter the tritium overflow produced by these stimuli. However, higher doses of diltiazem (60juM) reduced the tritium overflow elicted by RNS or Vt but enhanced that caused by KCI. The renal vasoconstriction produced by RNS, Vt and KCI as well as by exogenous NA was inhibited by low and high doses of nifedipine and diltiazem. 5 These data suggest that (a) RNS, Vt and KCl enhance the release of adrenergic transmitter by promoting the influx of Ca2+ into the nerve terminal through specific Ca2+ channels, probably N-type Ca2+ channels that are distinct from those located in the vascular smooth muscle and (b) co-CgTx could be a useful tool to differentiate between Ca2+ channels at the adrenergic nerve terminal and vascular smooth muscle.

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Effects of Verapamil on [3H]Norepinephrine Release

Cited by 15 publications

References 0 publications

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

Inhibition of noradrenaline release by ω‐conotoxin GVIA in the rat tail artery

Differential effect of ω‐conotoxin on release of the adrenergic transmitter and the vasoconstrictor response to noradrenaline in the rat isolated kidney

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