Direct inhibitory effects of some ‘calcium‐antagonists’ and trifluoperazine on the contractile proteins in smooth muscle

In guinea‐pig isolated taenia caeci and trachealis bathed in a K+‐rich, Ca2+‐free medium, CaCl2 (0.01–10 mm) produced a concentration‐dependent contraction. Zn2+ (0.01–1 mm), Cd2+ (0.01–1 mm), verapamil (0.01–100 μm) and trifluoperazine (1–100 μm) were effective antagonists of CaCl2‐induced responses. Zn2+ and Cd2+ in concentrations from 0.01 to 1 mm were without effect on the tone of taenia and trachea in normal Tris solution. Conversely, Zn2+ and Cd2+, in concentrations of 1 mm, caused contraction of these tissues in a K+‐rich, Ca2+‐free medium. Zn2+ (1 mm)‐induced contractions of taenia and trachea were completely inhibited by verapamil (10 μm). In taenia and trachea skinned of their plasma membranes, tension development induced by Ca2+ (10 μm or 1 μm, respectively) was unaffected by verapamil (100 μm), whereas trifluoperazine (100 μm) depressed the maximal tension produced by Ca2+. Segments of skinned preparations contracted in response to low concentrations of Zn2+ (10 μm) or Cd2+ (10 μm). It is concluded that Zn2+ may suppress Ca2+‐induced spasm by a direct action on the binding sites of the Ca2+ channel.

Section: Discussionsupporting

confidence: 68%

Antagonism of calcium by zinc in guinea‐pig isolated taenia caeci and trachealis muscle

Sarriá

Cortijo

Martı́-Cabrera

et al. 1989

“…Furthermore, the sensitivity to Ca2+ in the presence of It has been shown using skinned fibres ofthe guineapig taenia coli that verapamil (up to 100 gM) has no effect on the contractile machinery (Spedding, 1983). When the verapamil concentration is more than 10 pm, it may affect smooth muscle muscannic receptors (Cheng et al, 1985), or cardiac muscle sarcoplasmic function (Entman et al, 1972;Watanabe & Besch, 1974;Colvin et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

Effects of verapamil on the response of the guinea‐pig tracheal muscle to carbachol

Baba

Satake

Takagi

et al. 1986

1 The effects of verapamil on the contraction of the guinea-pig tracheal smooth muscle induced by calcium (Ca2") or barium (Ba2") were investigated in three different conditions: (a) in excess K solution, (b) in the presence ofcarbachol, and (c) in excess K solution containing carbachol. In order to clarify the contractions, the effects of removal and readdition of the divalent cations were also investigated. 2 In Ca2+-loaded tissues, application of carbachol in Ca-free medium produced a transient contraction, the magnitude of which decreased the longer the duration of exposure to Ca2+-free solution.3 In Ca2+-depleted, Ba2+-loaded tissues, application of carbachol in a Ba2+-and Ca2+-free medium produced a transient contraction the magnitude ofwhich decreased the longer the duration ofexposure to the Ba2+-and Ca2+-free solution. 4 After exposure to Ca2 -free solution for 40 min, the sensitivity of the tissue to Ca2+ was greater in the presence of 30 jAM carbachol (ED50 = 0.06 mM) than in the presence of40 mM K+ (ED-=0.3 mM).The Ca2+-sensitivity in the presence of 30 gAM carbachol plus K+ (40 mM) was not different from that in

“…The present study indicates that ketamine, like papaverine and theophylline, competitively blocks calcium-induced contractions in the K+-depolarized uterus of the rat. To assess the effects of the Ca2" antagonists on the influx of Ca2" through voltage-sensitive channels (Goodfraind et al, 1968;Weiss, 1981) (Spedding, 1983) another set of experiments compared the relaxation induced by these drugs in strips previously contracted with CaCl2 (1 mM) (Hof & Vuarela, 1983 Figure 1 shows the mean cumulative concentrationresponse curves for CaC12 alone and in the presence of a different concentrations of ketamine (0.3 to 3 mM), papaverine (3 to 30 gM), theophylline (0.1 to 1 mM) and verapamil (3 to 30 mM). Each drug produced a parallel and concentration-dependent rightward displacement of the dose-response curve to CaCI2 without significantly reducing the maximal response.…”

Section: Introductionmentioning

confidence: 99%

Ketamine‐inhibition of calcium‐induced contractions in depolarized rat uterus: a comparison with other calcium antagonists

Calixto

Loch

1985

1 The inhibitory effect of the intravenous anaesthetic ketamine on CaCl2-induced contractions in the isolated K+-depolarized uterus of the rat in Ca2+-free medium was compared with that produced by papaverine, theophylline and the calcium entry blocker verapamil.2 Pre-incubation for 20 min with either ketamine (0.3 to 3 mM), papaverine (3 to 30 IpM), theophylline (0.1 to mM) or verapamil (3 to 30 nM) induced parallel, concentration-dependent rightward displacements of the dose-response curves to Ca2+ (0.04 to 22 mM). The antagonism was competitive, except that due to verapamil, the Schild plot for which yielded a slope which differed significantly from unity. The calculated pA2 values (± s.e.mean) were: ketamine 3.90 ± 0.07; papaverine 5.55 ± 0.05; theophylline 3.99 ± 0.1 and verapamil 9.54 ± 0.24 3 These drugs differed in their ability to relax the sustained contraction induced by Ca2" (1 mM) in K+-depolarizing solution. Ketamine and verapamil relaxed the preparation in a concentrationdependent manner whereas theophylline and especially papaverine were less potent and induced only partial maximal relaxation. The tj of the relaxant effect was significantly less for ketamine than for verapamil (5 and 22 min, respectively). Only ketamine produced a relaxation comparable to that obtained by washing the preparation with Ca2+-free solution (t1 = approx. 5 min). 4 Prior exposure of the depolarized uterine strip to a low concentration of Ca2+ (0.22 mM) increased the potency of ketamine, but decreased that of papaverine and theophylline, in antagonizing Ca2+-induced contractions. In contrast, this procedure did not affect the potency of verapamil. 5 The inhibitory effects of these drugs, excluding those of verapamil, were completely reversed after washing the preparations with a high-potassium Ca2+-free solution, 3-5 times for about 30-60 min. 6 These experiments provide further evidence that the relaxant effect produced by ketamine on the rat isolated uterus is due to its ability to antagonize Ca2+ movements competitively and also show that there are marked differences between the nature of the relaxant effects of ketamine and those of papaverine, theophylline and verapamil.