Study of the mechanism of the relaxant action of (+)‐glaucine in rat vas deferens

Orallo, Francisco; Alzueta, Alejandro Fdez; Loza, Mabel; Vivas, Nuria M.; Badı́a, Albert; Campos, Manuel; Honrubia, M.; Cadavid, Marı́a Isabel

doi:10.1111/j.1476-5381.1993.tb13904.x

Cited by 16 publications

(17 citation statements)

References 25 publications

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“…Similar Ca2+-antagonist properties have been described in rat cerebral cortex (where (+ )-glaucine inhibits [3H]-( + )-cis-diltiazem binding, Ivorra et al, 1992). In rat vas deferens, (+)-glaucine has been characterized as an agent with weak relaxant activity, possibly due to its Ca2"-antagonist and non-selective a-adrenoceptor blocking properties (Orallo et al, 1993). The vasorelaxant action of (+)-glaucine in rat aorta seems to be related to o,-adrenoceptor blocking properties because it relaxes the contractile response induced by noradrenaline (NA) more strongly than that induced by K+ (Ivorra et al, 1992;Loza et al, 1993).…”

Section: Introductionmentioning

confidence: 63%

“…In fact, in anaesthetized normotensive rats, this alkaloid showed a hypotensive activity accompanied by a significant decrease in heart rate (Fdez. Alzueta et al, 1992a) the mechanism of which, though not extensively studied and clarified as yet, may be basically related to its in vitro vasodilator effect on the vascular smooth muscle, as has been previously described by Loza et al (1993).…”

Section: Introductionmentioning

confidence: 81%

“…This effect, which would exclude a possible intracellular action (see below), may be due to an antagonism of postsynaptic a1-adrenoceptors, previously described in rat vas deferens by Orallo et al (1993) and in rat cerebral cortex by Ivorra et al (1992). Otherwise, the fact that pD' values for (+)-glaucine were similar for contractions induced by 5-HT (in normal Krebs) and Ca2+ (in depolarizing calcium-free solution), would also tend to suggest: (1) that the alkaloid may display an intracellular activity and (2) the existence of a non-selective mechanism of (+)-glaucine action on the cell membrane, involving the blockade of Ca2+ influx through both voltagedependent and receptor-operated Ca2+ channels and/or the opening of K+ channels.…”

Section: Rat Isolated Atriamentioning

confidence: 99%

“…The experimental protocol followed was the one described in Orallo et al (1993) using Krebs bicarbonate solution (containing 1.5 mM instead of 2.5 mM CaCl2.2H20). The vasoconstrictor agents used were NA (10 gM), 5-HT (100 gM) and K+ (50mM).…”

Section: Ca+ Influxmentioning

confidence: 99%

“…In rat vas deferens, (+)-glaucine has been characterized as an agent with weak relaxant activity, possibly due to its Ca2"-antagonist and non-selective a-adrenoceptor blocking properties (Orallo et al, 1993). The vasorelaxant action of (+)-glaucine in rat aorta seems to be related to o,-adrenoceptor blocking properties because it relaxes the contractile response induced by noradrenaline (NA) more strongly than that induced by K+ (Ivorra et al, 1992;Loza et al, 1993). Furthermore, similar results have been obtained in rat cerebral cortex, where (+ )-glaucine blocks [3H]-prazosin binding (Ivorra et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

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Study of the in vivo and in vitro cardiovascular effects of (+)‐glaucine and N‐carbethoxysecoglaucine in rats

Orallo

Alzueta

Campos‐Toimil

et al. 1995

British J Pharmacology

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1 The cardiovascular and vasorelaxant effects of (+)-glaucine and of a semisynthetic derivative (N-carbethoxysecoglaucine) were studied in rats. 2 N-carbethoxysecoglaucine did not modify either systolic arterial pressure or heart rate values in conscious (25 mg kg-', p.o.) and anaesthetized normotensive rats (5 mg kg ', i.v.) 3 In conscious normotensive rats, oral administration of (+)-glaucine (25 mg kg-') did not modify either systolic arterial pressure or heart rate.4 In anaesthetized normotensive rats, (+)-glaucine (5 mg kg-', i.v.) produced a remarkable fall in mean arterial pressure (MAP) accompanied by a significant decrease in heart rate. In the same preparation, (+ )-glaucine (5 mg kg-', i.v.) did not modify the cardiovascular effects induced by noradrenaline (NA) (5 Ag kg-') and 5-hydroxytryptamine (5-HT) (300 1tg kg-') but markedly inhibited those induced by nicotine (200 Ig kg-').5 In isolated intact aorta of rat, (+)-glaucine (0.15-5tiM) competitively inhibited the contractions induced by NA (with a pA2 value of 7.14) and non-competitively those induced by 5-HT (in normal Krebs solution) and Ca2+ (in depolarizing Ca2+-free high-K+ 50 mM solution), with depression of the maximal response and with pD2' values of 5.56 and 5.26, respectively. 6 In experiments in Ca2+-free medium, (+)-glaucine (3 JAM) inhibited the contractions induced by NA and had no effect on either 5-HT-or caffeine-induced contractions. 7 Furthermore, in the experiments with radioactive Ca2+, (+)-glaucine (3 JAM) did not modify the basal uptake of 45Ca2+ but strongly inhibited the influx of 45Ca2+ induced by NA, 5-HT and K+. 8 (+)-Glaucine (5JM) had no effect on rate and force of contraction in rat isolated atria. 9 These results indicate that: (a) the cardiovascular effects (hypotension and bradycardia) of (+)-glaucine in anaesthetized normotensive rats (5 mg kg-') may be due, at least in part, to a ganglioplexic effect; (b) the vasorelaxant action of ( + )-glaucine (0.15-5 JM) in rat isolated aorta can be attributed to an a,-adrenoceptor blocking property (which may explain its inhibition of noradrenaline-induced 45Ca2+ influx and contractions in normal Krebs solution and noradrenaline-induced contractions in Ca2+-free medium) and to a Ca2+-antagonist activity (which may be responsible, at least in part, for the inhibition of 45Ca2+ uptake induced by NA, 5-HT and K+ and the contractions induced by both NA and 5-HT in normal Krebs solution and by Ca2+ in Ca2+-free high-K+ medium) and (c) there is no correlation between the mechanisms of action observed for (+ )-glaucine in vivo and in vitro, which suggests that the vasorelaxant activity of this alkaloid does not contribute to its hypotensive activity.

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Section: Introductionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 81%

Section: Rat Isolated Atriamentioning

confidence: 99%

Section: Ca+ Influxmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Study of the in vivo and in vitro cardiovascular effects of (+)‐glaucine and N‐carbethoxysecoglaucine in rats

Orallo

Alzueta

Campos‐Toimil

et al. 1995

British J Pharmacology

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Modes of Action of Defensive Secondary Metabolites

Wink

Schimmer

2018

Annual Plant Reviews Online

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Molecular Modes of Action of Defensive Secondary Metabolites

Wink¹,

Schimmer²,

Roberts³

et al. 2018

Annual Plant Reviews Online

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Secondary metabolites (SM) have been shaped by evolution for more than 500 million years. As a result, many of them have distinctive biochemical and pharmacological properties. The molecular modes of action of the main groups of SM are reviewed in this chapter. Details are given on interactions of SM with proteins that can induce conformational changes and thus a modification of their bioactivity. The fluidity and permeability of biomembranes constitute another important target, which is influenced by many lipophilic and amphiphilic SM. A number of SM can either alkylate or intercalate DNA, which can cause mutations and in consequence cancer or malformations. Many SM are cytotoxic because they interfere with biomembranes, proteins of the cytoskeleton or DNA; they often induce programmed cell death (apoptosis). A large number of SM, especially alkaloids modulate neuronal signal transduction by interfering with ion channels, ion pumps, neuroreceptors, choline esterase, monoamine oxidase and other enzymes related to signal transduction pathways. A typical feature of SM is their ability to modulate more than one molecular target; thus, additive and even synergistic activities can be expected.

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Study of the mechanism of the relaxant action of (+)‐glaucine in rat vas deferens

Cited by 16 publications

References 25 publications

Study of the in vivo and in vitro cardiovascular effects of (+)‐glaucine and N‐carbethoxysecoglaucine in rats

Study of the in vivo and in vitro cardiovascular effects of (+)‐glaucine and N‐carbethoxysecoglaucine in rats

Modes of Action of Defensive Secondary Metabolites

Molecular Modes of Action of Defensive Secondary Metabolites

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