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PubMed1991

The role of calcium channel blockers in the treatment of essential hypertension.

Calcium channel blockers, originally developed for the treatment of angina and supraventricular arrhythmias, have been shown to lower elevated blood pressure effectively in hypertensive patients. Verapamil, nifedipine, and diltiazem represent prototype compounds for unique chemical classes with differing pharmacologic properties. These drugs lower elevated blood pressure with efficacy comparable with other commonly used antihypertensives. Combination therapy with other agents usually results in an additive response. Side effects are usually mild and reversible and usually are an extension of the drug's pharmacologic effects. Moreover, adverse metabolic effects on lipid, glucose, or potassium levels are not common. Because of the excellent antihypertensive effects of calcium channel blockers and their potential importance in a variety of other disease states, these agents should be routinely considered for use as a first-line antihypertensive agent in appropriately selected patients with hypertension of any severity as part of a comprehensive plan to minimize cardiovascular risk.

Animals↗
PubMed1987

Comparative renal effects of calcium channel blockers in conscious spontaneously hypertensive rats.

Five calcium channel blockers with diverse chemical structures were studied for potential renal selectivity after oral administration of a single dose to conscious spontaneously hypertensive rats. Nitrendipine (3 and 10 mg/kg) and diltiazem (30 and 100 mg/kg) caused significant increases in sodium and water excretion. In comparison, prenylamine (100 and 300 mg/kg) and flunarizine (100 and 300 mg/kg) failed to augment sodium and water excretion. Verapamil caused significant natriuresis only at 30 mg/kg. These data suggest that the diuretic and natriuretic action is not a common property of all calcium channel blockers. Pretreatment with SCH 23390 (20 mg/kg), a dopamine DA1 antagonist, selectively attenuated the diuresis and natriuresis induced by high doses of diltiazem (100 mg/kg) and nitrendipine (10 mg/kg) without blocking the renal responses to hydrochlorothiazide (1 mg/kg). Similarly, reserpinization abolished the renal but not the hypotensive action of diltiazem. Pretreatment with indomethacin (10 mg/kg), a cyclooxygenase inhibitor also significantly attenuated the diuresis and natriuresis elicited by diltiazem (100 mg/kg). These data suggest that intact dopamine and prostaglandin systems in the kidney are required for optimal expression of the renal effects of diltiazem and nitrendipine.

Animals↗
PubMed1998

Calcium channel blockers, cancer incidence, and cancer mortality in a cohort of U.S. women: the nurses' health study.

BACKGROUND: Some studies have suggested that the use of calcium channel blockers may increase the risk of cancer. A possible association of the use of calcium channel blockers with cancer incidence and cancer mortality was addressed using data from the Nurses' Health Study. METHODS: In this study, a total of 18,635 female nurses reported regularly taking at least 1 of 4 cardiovascular medications in 1988: diuretics, beta-blockers, calcium channel blockers, and/or angiotensin-converting enzyme (ACE) inhibitors. Cancer incidence and cancer deaths were ascertained until 1994. RESULTS: During 6 years of follow-up, 852 women were newly diagnosed with cancer and 335 women died of cancer. Women who reported the use of calcium channel blockers had no increased risk of newly diagnosed cancer compared with those taking other cardiovascular drugs (relative risk=1.02; 95% CI 0.83-1.26). The relative risk of dying from cancer associated with the self-reported use of calcium channel blockers was 1.25 (95% CI 0.91-1.72). Relative risks were adjusted for the following self-reported factors: age; weight; height; cholesterol level; systolic and diastolic blood pressure; smoking; alcohol intake; physical activity; menopausal status; postmenopausal hormone use; aspirin use; and history of diabetes, cancer, stroke, myocardial infarction, coronary artery bypass graft or percutaneous transluminal coronary angioplasty, angina, and hypertension. Regarding site specific cancer incidence and mortality, only lung cancer incidence was somewhat increased (RR=1.61; 95% CI 0.88-2.96). CONCLUSIONS: These data suggest no important increase in overall cancer incidence or cancer mortality related to the self-reported use of calcium channel blockers.

Adrenergic beta-Antagonists↗
PubMed2004

Maintenance therapy with calcium channel blockers for preventing preterm birth after threatened preterm labour.

BACKGROUND: Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. OBJECTIVES: To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register (31 March 2004); MEDLINE (1966 to March 2004) and DARE (June 2003). SELECTION CRITERIA: Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with alternative drug therapy, placebo or no treatment. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the selection criteria, extracted data from the included study and assessed study quality. MAIN RESULTS: One trial of 74 women was included. No difference in the incidence of preterm birth was found when calcium channel blocker (nifedipine) maintenance therapy was compared with no treatment. Twenty-five women out of 37 in each group gave birth before 37 weeks (relative risk 1.00, 95% confidence interval 0.73 to 1.37). The trial did not report stillbirths and neonatal deaths prior to discharge. Neurological follow up of the infants was not addressed. REVIEWERS' CONCLUSIONS: The role of maintenance therapy with calcium channel blockers for preventing preterm birth is not clear. Well designed randomised trials of sufficient size with relevant outcomes are required.

Calcium Channel Blockers↗
PubMed1993

[The effect of calcium channel blockers in experimental myocardial infarct in rats].

The effect of the blockers of calcium channels on the development of myocardial ischaemia in rats with an occlusion of the coronary artery was examined. An occlusion of the coronary artery was carried out in rats anaesthetized with pentobarbital by tightening the ends of the ligature freely placed under the left coronary artery - ramus interventricularis seven days prior to ligation. The ischaemia-induced changes in the R-wave and ST-segment were recorded using ECG. The occlusion of the coronary artery produced arrhythmias, a significant elevation of the ST-segment and a slight increase in the heart rate. The blockers of calcium channels with different pharmacological properties - verapamil, nifedipine and diltiazem influenced the ischaemia-induced changes with different intensity. Nifedipine (0.02 mg.kg-1, i.v., 30 min prior to occlusion), verapamil (0.2 mg.kg-1, i.v., 10 mins prior to ischaemia), and diltiazem (0.3 mg.kg-1, i.v., 10 mins prior to ischemia) significantly reduced the increased elevation of the ST-segment. The highest effect on the above-mentioned model was shown by verapamil.

Animals↗
PubMed2002

Combination treatment with a calcium channel blocker and an angiotensin blocker in a rat systolic heart failure model with hypertension.

The mechanism and treatment of hypertensive systolic heart failure are not well defined. We compared the effect of an angiotensin-converting enzyme inhibitor (cilazapril, 10 mg/kg), an angiotensin receptor blocker (candesartan, 3 mg/kg), a calcium channel blocker (benidipine, 1, 3 or 6 mg/kg), and the same calcium channel blocker combined with renin-angiotensin blockers on systolic heart failure in Dahl salt-sensitive (DS) rats. DS rats were fed an 8% Na diet from 6 weeks of age and then subjected to the above drug treatments. Benidipine (1 mg/kg), cilazapril, and candesartan had compatible hypotensive effects and similar beneficial effects on cardiac hypertrophy, gene expression, and survival rate. The combination of benidipine with cilazapril or candesartan was found to have no additional beneficial effects on the above parameters, with the exception of a reduction in atrial natriuretic polypeptide gene expression. On the other hand, candesartan normalized serum creatinine, but serum creatinine was unaffected by either benidipine at 1 or 3 mg/kg or cilazapril. Further, the combined use of benidipine and either candesartan or cilazapril resulted in an additional reduction of urinary albumin excretion in DS rats. Thus systolic heart failure in DS rats is mainly mediated by hypertension, while renal dysfunction of DS rats is due to both hypertension and the AT1 receptor itself. These findings suggest that the combination of a calcium channel blocker with an AT1 receptor blocker or ACE inhibitor may be more effective in treating the renal dysfunction associated with systolic heart failure than monotherapy with either agent alone. However, further studies will be needed before reaching any definitive conclusion on the efficacy of this combination therapy in patients with heart failure.

Angiotensin Receptor Antagonists↗
PubMed1986

Pharmacodynamic profiles of different calcium channel blockers.

The cardiovascular effects of different calcium channel blockers (CCB), exemplified by nifedipine, verapamil and diltiazem, are not identical. Some of these differences in effect may be due to the different CCBs interacting with different calcium channel subtypes in the tissues, and/or that the drug-receptor sites are separate. The drugs also have different abilities to activate the sympathetic nervous system, nifedipine increasing and diltiazem decreasing the baroreflex sensitivity. Verapamil, but not nifedipine and diltiazem, has a postjunctional alpha-adrenoceptor blocking effect, and can also increase the release of noradrenaline from adrenergic nerves by blocking pre-junctional alpha-adrenoceptors. In addition, verapamil may have a reserpine-like action on sympathetic nerves. The vasodilator actions of CCBs are not uniform, but seem to vary between species, different vascular regions, and different agents. Mechanisms other than blockade of influx of calcium from the extracellular medium have been suggested to explain these differences, including inhibition of intracellular calcium release, blockade of postjunctional alpha-adrenoceptors, interaction with calmodulin, inhibition of cyclic AMP phosphodiesterase, stimulation of Na+-, K+-activated ATPase, stimulation of a calcium pump, and a direct interaction with the contractile proteins. The heterogeneity in pharmacodynamic profile characterizing the CCBs is conspicuous, and may be of importance when selecting agents for the treatment of various cardiovascular and non-cardiovascular disorders.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2004

Neuroprotection in the rat lateral fluid percussion model of traumatic brain injury by SNX-185, an N-type voltage-gated calcium channel blocker.

Overload of intracellular calcium ([Ca(2+)](i)) following traumatic brain injury (TBI) has been implicated in the pathogenesis of neuronal injury and death. Voltage-gated calcium channels (VGCCs) provide one of the major sources of Ca(2+) entry into cells. Therefore, the potential neuroprotective activity of SNX-185, a specific N-type VGCC blocker, was tested in rats using the lateral fluid percussion (LFP) model of TBI. SNX-185 (50, 100, or 200 pmol) or vehicle was injected 5 min after injury into the CA2-3 subregion of the hippocampus ipsilateral to TBI. Acute neuronal degeneration was visualized in brain sections 24 h postinjury using the histofluorescent marker Fluoro-Jade (FJ), and the number of surviving neurons in the CA2-3 subregion of the hippocampus 42 days after injury was determined stereologically. Behavioral outcome after TBI and drug treatment was assessed in the beam walk test and Morris water maze. Direct injection of SNX-185 into the CA2-3 region of the hippocampus reduced neuronal injury 24 h after TBI and increased neuronal survival at 42 days at each of the three drug concentrations. Behavioral outcome in both the beam walk and Morris water maze were also improved by SNX-185, with 100 and 200 pmol, but not 50 pmol SNX-185 providing neuroprotection. These data support previous studies demonstrating substantial neuroprotection after TBI by treatment with N-type VGCC blockers.

Animals↗
PubMed2005

Protective effects of an angiotensin II receptor blocker and a long-acting calcium channel blocker against cardiovascular organ injuries in hypertensive patients.

The purpose of this study is to compare the long-term effects of an angiotensin II receptor blocker (ARB) and a long-acting calcium channel blocker (CCB) on left ventricular geometry, hypertensive renal injury and a circulating marker of collagen synthesis in hypertensive patients. Patients with essential hypertension (24 men and 19 women; age, 37-79 years) were treated with a long-acting CCB, amlodipine (AML; 2.5-7.5 mg once daily) for 6 months. Then, AML was switched to an ARB, candesartan (CS; 4-12 mg once daily), in 22 patients (CS group), while AML was continued in the remaining 21 patients for another 6 months (AML group). At the end of each treatment period, ambulatory blood pressure monitoring (ABPM), echocardiography and sampling of blood and urine were performed. The average office blood pressure during the latter period was comparably controlled in the AML and the CS groups (AML: 130 +/- 8/87 +/- 7 mmHg; CS: 133 +/- 11/ 88 +/- 7 mmHg), while the average systolic blood pressure of 24-h ABPM was significantly lower in the AML than in the CS group (127 +/- 9 vs. 133 +/- 14 mmHg, p<0.05). Consequently, the left ventricular mass index was significantly decreased in the AML group (102 +/- 18 to 92 +/- 12 g/m2, p<0.05), while the change was insignificant in the CS group (103 +/- 25 to 98 +/- 21 g/m2). On the other hand, plasma procollagen I C-terminal peptide (PICP), a marker of collagen synthesis, was lowered by CS (86 +/- 21 to 70 +/- 21 ng/ml, p<0.01), but was not significantly affected by AML (80 +/- 127 to 74 +/- 91 ng/ml). CS reduced urinary albumin excretion (57 +/- 123 to 26 +/- 33 mg/g creatinine, p<0.05), but AML did not bring about significant changes (85 +/- 27 to 73 +/- 19 mg/g creatinine). The results suggested that long-acting CCBs are effective in improving left ventricular hypertrophy by controlling 24-h blood pressure, while ARBs possess protective effects against cardiovascular fibrosis and renal injury beyond their antihypertensive effects.

Adult↗
PubMedDate not supplied

Effects of calcium channel blockers on potassium homeostasis.

The known effects of calcium channel blockers on various aspects of potassium homeostasis are reviewed. Regulation of potassium homeostasis requires both renal and external handling mechanisms. Signaling by calcium appears to mediate both of these. Calcium channels have been identified in adrenal glomerulosa cells, and cellular calcium entry has been demonstrated in vitro to be necessary for the synthesis and secretion of aldosterone. Calcium channel antagonists such as verapamil and nifedipine, at pharmacologic doses, can block aldosterone production. In vivo, however, only chronic administration of verapamil appears to attenuate aldosterone responsiveness to angiotensin II. Chronic administration of nifedipine does not have a dramatic effect on aldosterone production following potassium loading. Other studies have demonstrated improved extrarenal potassium disposal following treatment with calcium channel blocking agents. Clinically, there are no reports of either hyperkalemia or hypokalemia with the routine therapeutic use of these agents given alone. This review was prompted by the development of hyperkalemia in a patient with chronic renal failure following the initiation of therapy with the calcium channel blocker diltiazem: however, numerous other etiologies may also have contributed to the development of hyperkalemia in this case. Review of the data indicates that current evidence implicating this class of drugs in the pathogenesis of disordered potassium regulation remains equivocal.

Adrenal Cortex↗
PubMed1999

Calcium channel blockers and mortality in elderly patients with myocardial infarction.

BACKGROUND: Although calcium channel blockers are a useful therapy in relieving angina, lowering blood pressure, and slowing conduction of atrial fibrillation, growing evidence has cast doubt on their safety in patients with coronary disease. OBJECTIVE: To examine the association between calcium channel blocker therapy at hospital discharge and mortality in a population-based sample of elderly patients hospitalized with acute myocardial infarction. DESIGN: Retrospective cohort study using data from medical charts and administrative files. SETTING: All acute care hospitals in 46 states. PATIENTS: All Medicare patients with a principal diagnosis of acute myocardial infarction consecutively discharged from the hospital alive during 8-month periods between 1994 and 1995 (N = 141,041). MAIN OUTCOME MEASURE: Mortality at 30 days and 1 year. RESULTS: Calcium channel blockers were widely prescribed at hospital discharge to elderly patients with myocardial infarction between 1994 and 1995 (n = 51,921), the most commonly prescribed being diltiazem (n = 21,175), nifedipine (n = 12,670), amlodipine (n = 11,683), and verapamil (n = 3639). After adjusting for illness severity and concomitant medication use, patients who were prescribed calcium channel blockers at hospital discharge did not have increased risk for 30-day or 1-year mortality, with the exception of the few (n = 116) treated with bepridil. Bepridil differs from other calcium channel blockers because of its tendency to prolong repolarization, and its association with proarrhythmic effects in elderly patients. CONCLUSION: We did not identify a mortality risk in a large consecutive sample of elderly patients with myocardial infarction, which supports the need for additional prospective trials examining calcium channel blocker therapy for ischemic heart disease.

Aged↗
PubMed1993

Combination drug therapy with calcium-channel blockers in the treatment of systemic hypertension.

Calcium-channel blockers have been shown to be both safe and effective for treatment of patients with systemic hypertension. These drugs reduce peripheral vascular resistance predominantly by the inhibition of transmembrane calcium ion fluxes in vascular smooth muscle, and by this mechanism can reduce elevated blood pressure. To maximize blood pressure lowering efficacy in patients, calcium-channel blockers have also been used in combination with other antihypertensive treatments that have included diuretics, beta-adrenergic blockers, and angiotensin-converting enzyme inhibitors.

Adrenergic beta-Antagonists↗
PubMed2000

Use of calcium channel blockers and risk of hospitalized gastrointestinal tract bleeding.

BACKGROUND: We conducted a case-control study of the association between calcium channel blocker use and gastrointestinal (GI) tract bleeding in hypertensive members of a health maintenance organization. METHODS: Case patients (n=174) were treated hypertensive health maintenance organization members hospitalized for GI tract bleeding between January 1992 and December 1994. Case patients were identified using computerized diagnosis codes and were confirmed by medical record review. Control subjects (n=771) were treated hypertensive members selected from ongoing studies at the health maintenance organization. Computerized pharmacy data and medical records were used to assess medication use and other risk factors for GI tract bleeding. RESULTS: Compared with beta-blocker users, calcium channel blocker users had an age-, sex- and calendar year-adjusted relative risk (RR) of GI tract bleeding of 2.60 (95% confidence interval [CI], 1.71-3.96). The RR associated with calcium channel blocker use was 2.05 (95% CI, 1.33-3.17) after further adjustment for number of recent visits, diastolic blood pressure, chronic congestive heart failure, and duration of hypertension. No significant dose-response relationship was observed. Compared with beta-blocker users, angiotensin-converting enzyme inhibitor users had an RR of 1.22 (95% CI, 0.75-1.97). Calcium channel blocker use tended to be more strongly associated with risk of lower GI tract bleeding (RR, 2.56; 95% CI, 1.08-6.05) than with risk of upper GI tract bleeding (RR, 1.54; 95% CI, 0.91-2.59) or peptic ulcer-related bleeding (RR, 1.17; 95% CI, 0.62-2.21), although these results were compatible with chance. CONCLUSIONS: Calcium channel blocker use might be associated with an elevated risk of GI tract bleeding. These findings require confirmation in randomized studies.

Adrenergic beta-Antagonists↗
PubMed1995

Maitotoxin-elicited calcium influx in cultured cells. Effect of calcium-channel blockers.

Maitotoxin elicited a marked influx of 45Ca2+ into NIH 3T3 fibroblast cells. The influx was blocked by imidazoles (econazole, miconazole, SKF 96365, clotrimazole, calmidazolium) with IC50 values from 0.56 to 3 microM. Phenylalkylamines (verapamil, methoxyverapamil) and nitrendipine were less potent, and diltiazem was very weak. Among other calcium blockers, the diphenylbutylpiperidines fluspirilene and penfluridol, the diphenylpropylpiperidine loperamide, and the local anesthetic proadifen were quite active with IC50 values of 2-4 microM. The pattern of inhibition of maitotoxin-elicited calcium influx did not correspond to the ability of the agents to block elevation of calcium that ensues through calcium-release activated calcium (CRAC) channels after activation of phosphoinositide breakdown by ATP in HL-60 cells. The imidazoles did block CRAC channels, but fluspirilene, penfluridol, loperamide and proadifen were ineffective. Loperamide actually appeared to enhance influx of calcium via the activated CRAC channels. The imidazoles, in particular calmidazolium, caused an apparent influx of calcium and caused a stimulation of phosphoinositide breakdown in HL-60 cells.

3T3 Cells↗
PubMed1983

[Mechanism of actions involved in improved effects of calcium channel blockers on ischemic myocardial conduction delay].

The effects of calcium channel blockers and lidocaine on changes in action potential characteristics and conduction time during exposure to altered Tyrode's solution imitating some of metabolic alterations that occur in acute myocardial ischemia (pO2 less than 50 mmHg, KCl 8 mM, pH 6.80) were examined in the isolated right ventricular epicardium of canine heart. The superfusion with altered Tyrode's solution produced loss of resting membrane potential (RMP), action potential amplitude (APA), action potential duration (APD), and upstroke velocity of action potential (Vmax), and prolonged conduction time (CT). In the presence of lidocaine (5 mg/l), altered Tyrode's solution aggravated the reductions of APA and Vmax, and of the prolongation of CT. On the other hand, in the presence of either verapamil (1 mg/l), diltiazem (3 mg/l), nifedipine (1 mg/l), or Ni2+ (1 mM), the degree of the reductions of APA and Vmax and of the prolongation of CT induced by altered Tyrode's solution was reduced. However, neither lidocaine nor calcium channel blockers affected change in RMP. These results suggest that decreasing calcium influx during ischemia improves depressed sodium channel, and this effect can partly explain the improvement of ischemia-induced conduction delay by calcium channel blockers.

Action Potentials↗
PubMed1995

Myocardial protection with calcium-channel blockers during ischaemia and reperfusion by PTCA.

The effects of calcium channel blockers on acute myocardial ischaemia have been evaluated over the past two decades. A number of experimental studies have demonstrated that calcium antagonists protect the myocardium when administered before or during PTCA. Intracoronary verapamil prior to the second inflation attenuates the severity of ischaemic ST-segment changes and anginal pain. Heart rate and blood pressure are not influenced by verapamil or placebo. Similarly, there are multiple clinical and biological data suggesting that intracoronary nifedipine, diltiazem or bepridil, and intracoronary or intravenous nicardipine might result in a reduced incidence of myocardial ischaemia during PTCA. The beneficial effect of these drugs can be explained by a direct cardioprotective effect or by an enhanced collateral flow and haemodynamic improvement. During early reperfusion in acute myocardial infarction (AMI) administration of calcium channel blockers or agents that inhibit calcium release from the sarcoplasmic reticulum can protect hearts from stunning and can decrease the no-reflow phenomenon. The most recent explanation relates this observation to decreased sensitivity of the myofibrils to calcium. Further clinical and experimental studies are necessary to clarify the protective role in reperfusion injury. To summarize, therefore, administration of calcium channel blockers can decrease ischaemia during elective PTCA and can reduce reperfusion injury during early PTCA in AMI.

Angioplasty, Balloon, Coronary↗
PubMed1992

Myocardial stunning following coronary angioplasty: protective effects of calcium-channel blockers.

The beneficial effects of calcium-channel blockers against myocardial stunning have been tested in experimental studies, showing that, when added before or during ischemia, a protective effect against postischemia stunning is achieved. The present study was undertaken to test and compare the protective effect of calcium antagonists [nisoldipine (NIS) and nifedipine (NIF)] and nitrates (NIT) against myocardial stunning in patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) with prolonged inflation as PTCA represents a model of induced acute and severe ischemia for a brief period and might cause myocardial stunning. The study included 30 patients between the ages of 42 and 67 years, all with exercise-induced angina and single-vessel disease, with severe stenosis (80% to subtotal occlusion) localized on the left anterior descending artery and with the absence of collaterals on the coronary angiograms. Moreover, all patients had normal left ventricular (LV) overall function, as well as normal systolic thickening of the anterior wall, supplied by the diseased artery. Patients were randomized to a pre-PTCA treatment with NIT, 80-120 mg/day (10 patients), NIF, 40-60 mg/day (10 patients), and NIS, 10-20 mg/day (10 patients). Pre-PTCA treatment was initiated 7 days before the procedure and continued after. During the PTCA, at the first balloon inflation, an additional dose of 300 micrograms of NIT was injected into the left anterior descending artery through the balloon catheter in the patients in the NIT group, as well as 0.2 mg of NIF in NIF group patients and 0.05 mg of NIS in NIS group patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

The bovine cardiac receptor for calcium channel blockers is a 195-kDa protein.

The cardiac receptor for calcium channel blockers was purified from bovine microsomal membranes which contained 235 +/- 33 fmol nimodipine-binding sites/mg protein (mean +/- SEM of nine preparations). To identify the receptor during the purification 20% of its binding sites were prelabeled with (+)[3H]PN200-110. The receptor was solubilized with 0.6% digitonin and was purified to a specific density of 157 pmol/mg using a combination of ion-exchange, wheat-germ-agglutinin-Sepharose chromatography and sucrose density gradient centrifugation. In the last sucrose gradient bound (+)[3H]PN200-110 comigrated with a 195-kDa protein. ( +/-)[3H]Azidopine and [3H]ludopamil, the photoaffinity ligands for the dihydropyridine and phenylalkylamine-binding site of the calcium channel, were incorporated specifically into the 195-kDa protein. These data indicate that the bovine cardiac receptor for calcium channel blockers is a 195-kDa protein. Its molecular mass suggests that the bovine cardiac receptor differs considerably from the rabbit skeletal muscle receptor protein for calcium channel blockers.

Affinity Labels↗