Effects of Ca Antagonists on the Norepinephrine Release and Contractile Responses of Isolated Canine Saphenous Veins to High KCl

Takata, Yoshinobu; Kato, Harubumi

doi:10.1254/jjp.34.397

Cited by 24 publications

(31 citation statements)

References 21 publications

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“…This merits further examination. (Takata & Kato, 1984), rat tail artery and guinea-pig vas deferens (Wolchinsky & Zsoter, 1985) the other hand, the granular uptake mechanism for adenosine is reserpine-insensitive and may be independent ofthat for NA (Winkler et al, 1981). Although its basis was not investigated, this mechanism could account for the increased response to evoked transmitter observed in the presence of low concentrations of verapamil (French & Scott, 1981;Bornstein et al, 1985) and nifedipine (Bornstein et al, 1985).…”

Section: Action Potential Conductionmentioning

confidence: 99%

Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea‐pig vas deferens

Beattie

Cunnane

Muir

1986

British J Pharmacology

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The effects of the Ca2+ channel antagonists amlodipine, cobalt, diltiazem, nifedipine and verapamil and the local anaesthetic lignocaine were investigated on action potential conduction in and on evoked transmitter release from sympathetic nerves in the guinea‐pig isolated vas deferens. Transmitter release was investigated by measurement of (a) evoked (trains of pulses at 1 and 2 Hz, 0.1‐0.5 ms supramaximal voltage) excitatory junction potentials (e.j.ps) using microelectrodes; tension was recorded simultaneously; (b) tritium (3H) overflow from vasa preincubated (37°C, 30 min) in Krebs solution containing either [3H]‐noradrenaline (NA, 25 μCi ml−1, 2 × 10−6 M NA) or [3H]‐adenosine (50 μCi ml−1, 1 × 10−6 M adenosine). Amlodipine (0.5–2 × 10−4 M), verapamil (0.5‐2 × 10−4 M), diltiazem (1–8 × 10−4 M), lignocaine (0.1–2 × 10−3 M) and cobalt (2–6 × 10−2 M) in descending order of potency, but not nifedipine (1–5 × 10−3 M), increased the latency and inhibited, then abolished, the amplitude and number of action potentials in a concentration‐dependent manner. Amlodipine (0.5–1 × 10−4 M), verapamil (1–2 × 10−4 M), diltiazem (1–5 × 10−4 M) and cobalt (1 × 10−3 M), in descending order of potency, but not nifedipine (5 × 10−4 M), inhibited then abolished evoked e.j.ps in a concentration‐dependent manner. Cobalt inhibited e.j.ps at a lower concentration than that (2–6 × 10−2 M) required to block action potential conduction. In unstimulated tissues, the resting 3H overflow following preincubation with [3H]‐NA consisted largely of 4‐hydroxy 3‐methoxymandelic acid (VMA), 4‐hydroxy 3‐methoxy phenylglycol (MOPEG), 3,4 dihydroxyphenylglycol (DOPEG) and NA; stimulated tissues (300 pulses at 20 Hz, 0.5 ms supramaximal voltage) released mainly NA. Verapamil (0.1–1 × 10−4 M), amlodipine (0.05–1 × 10−4 M) and nifedipine (1–5 × 10−4 M), but not cobalt (2 × 10−3 M), increased, significantly, the resting overflow of 3H comprising mainly DOPEG. Cobalt (2 × 10−3 M) inhibited, significantly, the stimulation‐evoked overflow of 3H. Verapamil (1 × 10−4 M) had little effect on the resting overflow of 3H following preincubation with [3H]‐adenosine. Diltiazem (5 × 10−4 M) and cobalt (2 × 10−3 M) both inhibited evoked 3H overflow. Nifedipine (5 × 10−4 M) was ineffective. The effectiveness of Ca2+ channel antagonists at pre‐ and postjunctional sites differ; the results are discussed in terms of the selectivity of these drugs for each site and their differential effects on transmitter release.

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Section: Action Potential Conductionmentioning

confidence: 99%

Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea‐pig vas deferens

Beattie

Cunnane

Muir

1986

British J Pharmacology

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“…It is known that an increased influx of Ca2" into neurotransmitter release produced by transmural adrenergic nerve endings triggers the neurotransmitter nerve stimulation (TNS) from isolated canine saphenrelease evoked by electrical stimulation (Blaustein, ous veins (Takata & Kato, 1984). Similar results were 1979).…”

Section: Introductionmentioning

confidence: 71%

“…The procedures used for obtaining, incubating and superfusing helical strips of the saphenous veins have been described previously in detail (Takata & Kato, 1984). Briefly, the strips (3 x 30 mm) were incubated for 2 h with Krebs-bicarbonate (Krebs) solution containing (-)-[7_3HI-noradrenaline, 8 x 10-8 M (10 pCi in 5 ml of incubation medium) and ascorbic acid 5.7 x 10-5 M, and mounted for superfusion.…”

Section: Isotope Experimentsmentioning

confidence: 99%

“…The effects of the Ca antagonists on both TNSevoked tritium overflow and contraction in the presence of 4-AP were estimated from the ratio S6/S3 for the reason given in the previous report (Takata & Kato, 1984), and they were compared with the corresponding ratio obtained from the superfusion with 4-AP alone without the Ca antagonists. Radioactivity obtained from the 2 min sample just before S2-S6 was considered as the spontaneous overflow of total tritium and designated as Sp2-Sp6, respectively.…”

Section: Isotope Experimentsmentioning

confidence: 99%

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Differential effects of Ca antagonists on the noradrenaline release and contraction evoked by nerve stimulation in the presence of 4‐aminopyridine

Kato¹,

Takata²

1987

British J Pharmacology

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We previously reported that verapamil, nicardipine and diltiazem inhibited both neurotransmitter release and contraction evoked by transmural nerve stimulation (TNS) in the canine saphenous vein. To evaluate whether the three Ca antagonists act on the nerve endings by inhibiting Ca2+ influx, the effects of the three antagonists were studied in the presence of 4‐aminopyridine (4‐AP) 3 × 10–4 m on the TNS‐evoked tritium overflow and contraction of canine saphenous veins preloaded with [3H]‐noradrenaline. 4‐AP increased both tritium overflow and contraction evoked by TNS, but did not enhance the contraction induced by exogenous noradrenaline (10 nmol). In the veins pretreated with 4‐AP, verapamil (3 × 10–5 m) and nicardipine (10–5 m and 3 × 10–5 M) caused no significant effects on the TNS‐evoked tritium overflow, but they still inhibited the contraction. Diltiazem (10–5 m and 3 × 10–5 m) significantly inhibited both responses to TNS in the veins pretreated with 4‐AP, the effects being nearly equipotent to those in the absence of 4‐AP. The (–)‐cis isomer of diltiazem (10−5 m and 3 × 10−5 M), which is about 100 times less potent than diltiazem in inhibiting Ca2+ influx, inhibited both responses to TNS in the presence of 4‐AP to almost the same degree as diltiazem. When 4‐AP was added after the Ca antagonists, it reversed the TNS‐evoked tritium overflow inhibiting actions of verapamil (3 × 10−5 m) and nicardipine (3 × 10−5 m) much more effectively than that of diltiazem (3 × 10−5 m). Tetracaine (4 × 10−6 M) significantly inhibited the TNS‐evoked tritium overflow and contraction, which were unaffected by 4‐AP. Sodium salicylate (10−2 M) failed to modify the inhibition of TNS‐evoked tritium overflow following diltiazem (3 × 10−5 M), but it enhanced that of tetracaine (4 × 10−6 M). Verapamil but not diltiazem and nicardipine significantly increased the spontaneous tritium overflow from veins pretreated with 4‐AP. The present study together with previous results suggests that diltiazem but not verapamil and nicardipine may inhibit the TNS‐evoked neurotransmitter release through an action other than inhibition of Ca2+ influx into the adrenergic nerve endings, allowing an inhibition of the resulting contraction.

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“…We previously reported that Ca antagonists inhibited the depolarization-evoked norepine phrine (NE) release from the adrenergic nerve endings (1,2). The concentration range of the Ca antagonists required to inhibit the NE release, however, appears to be con siderably higher than that needed to relax vascular smooth muscle (3), suggesting the possibility that Ca2+ channels in the adre nergic nerve endings may differ from those in vascular smooth muscle membrane.…”

mentioning

confidence: 99%

Effects of Bay K 8644 on the electrically evoked and KCl-evoked norepinephrine release and the corresponding contraction in isolated canine saphenous veins.

Takata

Kato

1987

Jpn.J.Pharmacol

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Abstract-Bay K 8644 caused no significant effects on the 3H overflow and con traction evoked by electrical stimulation in the canine saphenous vein preloaded with [3H]norepinephrine.Bay K 8644 significantly enhanced the 3H overflow evoked by 40 mM KCI in a concentration-dependent manner, which was antagonized by nisoldipine.Bay K 8644 failed to significantly augment the KCI-evoked con traction.These results suggest that there is a difference between the modes of action of Bay K 8644 on norepinephrine releases evoked by electrical stimulation and KCI.

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Effects of Ca Antagonists on the Norepinephrine Release and Contractile Responses of Isolated Canine Saphenous Veins to High KCl

Abstract: Abstract-Effects of verapamil, diltiazem and nicardipine on tritium overflow and contraction evoked by transmural nerve stimulation (TNS) were evaluated using canine saphenous vein strips preincubated with [

Cited by 24 publications

References 21 publications

Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea‐pig vas deferens

Effects of calcium channel antagonists on action potential conduction and transmitter release in the guinea‐pig vas deferens

Differential effects of Ca antagonists on the noradrenaline release and contraction evoked by nerve stimulation in the presence of 4‐aminopyridine

Effects of Bay K 8644 on the electrically evoked and KCl-evoked norepinephrine release and the corresponding contraction in isolated canine saphenous veins.

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