Review of Nisoldipine Binding Studies

Janis, R.A.; Shrikhande, Alka; Greguski, R; Pan, Mary; Scriabine, Alexander

doi:10.1007/978-3-642-73010-8_3

Cited by 8 publications

(3 citation statements)

References 17 publications

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“…It was also evident from our results that a proportion of cone HVA Ca channel current was insensitive to nifedipine and nisoldipine, even when these antagonists were applied at high nonspecific concentrations, after ample time had elapsed to exclude very slow actions of the antagonists, and when the blockers were tested from several holding potentials. The insensitivity of this current to these antagonists could be due to their lack of efficacy in cone photoreceptors, although, for example, nisoldipine shows very high efficacy in L-type Ca channel block compared with other dihydropyridine antagonists in other preparations (Janis et al, 1987). Thus, while our data do not exclude the possibility of an additional dihydropyridine-resistant HVA Ca channel component in cone photoreceptors, a more parsimonious explanation is that dihydropyridines are not fully efficacious in this cell type, and that even at concentrations shown to be saturating or nonspecific elsewhere, significant Ca channel current remains.…”

Section: Dihydropyridine-resistant Ca Channel Currentmentioning

confidence: 99%

The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.

Wilkinson

Barnes

1996

The Journal of General Physiology

112

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ABSTgACT High-voltage activated Ca channels in tiger salamander cone photoreceptors were studied with nystatin-permeabilized patch recordings in 3 mM Ca 2+ and 10 mMBa 2+. The majority of Ca channel current was dihydropyridine sensitive, suggesting a preponderance of L-type Ca channels. However, voltage-dependent, incomplete block (maximum 60%) by nifedipine (0.1-100 IzM) was evident in recordings of cones in tissue slice. In isolated cones, where the block was more potent, nifedipine (0.1-10 ~M) or nisoldipine (0.5-5 ~M) still failed to eliminate completely the Ca channel current. Nisoldipine was equally effective in blocking Ca channel current elicited in the presence of 10 mM Ba z+ (76% block) or 3 mM Ca 2+ (88% block). 15% of the Ba z+ current was reversibly blocked by 0~-conotoxin GVIA (1 p.M). After enhancement with 1 I*M Bay K 8644, t0-conotoxin GVIA blocked a greater proportion (22%) of Ba 2+ current than in control. After achieving partial block of the Ba 2+ current with nifedipine, concomitant application of t0-conotoxin GVIA produced no further block. The P-type Ca channel blocker, ~0-agatoxin IVA (200 nM), had variable and insignificant effects. The current persisting in the presence of these blockers could be eliminated with Cd 2+ (100 ~M). These results indicate that photoreceptors express an L-type Ca channel having a distinguishing pharmacological profile similar to the ~m Ca channel subtype. The presence of additional Ca channel subtypes, resistant to the widely used L-, N-, and P-type Ca channel blockers, cannot, however, be ruled out.

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Section: Dihydropyridine-resistant Ca Channel Currentmentioning

confidence: 99%

The dihydropyridine-sensitive calcium channel subtype in cone photoreceptors.

Wilkinson

Barnes

1996

The Journal of General Physiology

112

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“…In clogs, nisoldipine enhanced coronary collateral flow to poststenotic regions with a comparable distribution to the epicardial and endocardial layers [37 I. Whereas in previous clinical studies with intravenous nifedipine coronary blood flow was increased for only a couple of minutes [38,39], in the present study both dosages of nisoldipine caused a prolonged rise in coronary venous oxygen satm'ation, probably clue to a slower dissociation of nisoldipine fl'om the binding site [30,31].…”

Section: Discussionmentioning

confidence: 67%

“…Nisoldipine plasma levels determined at the time of the maxinlal coronary dilation corresponded to the values usually measured after oral administration of this drug [2.% ARer both dosages of nisoldipine, the dilation of epicardial coronary arteries tended to further increase, up to the end of the study period, despite declining plasma levels. Since no active metabolites of nisoldipine are known, this hysteresis seems to be a consequence of the high receptor affinity of the compound [30,31]. Due to the different courses of nisoldipine plasma levels and coronary dilation, correlation between these parameters at the individual measurement times was not possible.…”

Section: Discussionmentioning

confidence: 99%

Vasodilatory effects of nisoldipine on coronary arteries—Correlation with plasma levels

Jost

Rafflenbeul

Mogwitz

et al. 1990

Cardiovasc Drug Ther

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Vasomotion of angiographically normal and stenotic epicardial coronary arteries was analyzed up to 15 minutes after the onset of an intravenous infusion (4 minutes) of 0.5 mg (13 patients, group A) or 1 mg nisoldipine (13 patients, group B). After both doses the maximal increase of the mean diameters of normal coronary segments was achieved not before the 15th minute, averaging 11 +/- 6% in group A (p less than 0.001) and 18 +/- 9% in group B (p less than 0.001). Eleven of 15 and 8 of 9 coronary stenoses in groups A and B dilated to 5-80% and 15-70%, respectively. The nisoldipine concentration reached maximal levels at the end of the infusion (fourth minute) with an average of 8 +/- 4 ng/ml and 17 +/- 7 ng/ml in groups A and B, respectively. A significant correlation between nisoldipine plasma levels and dilation of normal coronary segments was obtained only with the individual maxima of these parameters and only in group A (p less than 0.01). The hysteresis of the coronary dilation in relation to the drug plasma levels may be due to the high receptor affinity of nisoldipine. In either group nisoldipine provoked a persistent increase in coronary sinus oxygen saturation (p less than 0.01) and a substantial and prolonged drop in systolic and diastolic aortic pressure (p less than 0.001). Both doses of nisoldipine induced a rise in heart rate (p less than 0.01) and a slight drop in the rate-pressure product (p less than 0.05).

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