The binding of [3H]nitrendipine to receptors for calcium channel antagonists in the heart, cerebral cortex, and ileum of rats

Ehlert, Frederick J.; Roeske, William R.; Itoga, Eiko; Yamamura, Henry I.

doi:10.1016/0024-3205(82)90293-4

Cited by 230 publications

(72 citation statements)

References 9 publications

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“…[ 3 H]Nitrendipine binding to cortical membranes was measured by a modification of the method of Ehlert et al (1982). The final pellet had been resuspended in 50mM Tris-HCl buffer (pH 7.4).…”

Section: [ 3 H]nitrendipine Bindingmentioning

confidence: 99%

Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

et al. 1993

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SUMMARY1. Chronic ingestion of caffeine by male NIH strain mice alters the density of a variety of central receptors.2. The density of cortical A 1 adenosine receptors is increased by 20%, while the density of striatal A 2A adenosine receptors is unaltered.3. The densities of cortical β 1 and cerebellar β 2 adrenergic receptors are reduced by ca. 25%, while the densities of cortical α 1 and α 2 adrenergic receptors are not significantly altered.Densities of striatal D 1 and D 2 dopaminergic receptors are unaltered. The densities of cortical 5 HT 1 and 5 HT 2 serotonergic receptors are increased by 26-30%. Densities of cortical muscarinic and nicotinic receptors are increased by 40-50%. The density of cortical benzodiazepine-binding sites associated with GABA A receptors is increased by 65%, and the affinity appears slightly decreased. The density of cortical MK-801 sites associated with NMDA-glutaminergic receptors appear unaltered.4. The density of cortical nitrendipine-binding sites associated with calcium channels is increased by 18%.5. The results indicate that chronic ingestion of caffeine equivalent to about 100 mg/kg/day in mice causes a wide range of biochemical alterations in the central nervous system.

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Section: [ 3 H]nitrendipine Bindingmentioning

confidence: 99%

Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

et al. 1993

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“…Voltage-dependent calcium channels that mediate functions of smooth muscle and cardiac muscle and neural tissue are blocked by calcium channel-antagonist drugs (15,16 (18,19). The DPBPs display structural similarities to verapamil-like drugs (Fig.…”

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confidence: 99%

Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.

Gould

Murphy

Reynolds

et al. 1983

Proc. Natl. Acad. Sci. U.S.A.

188

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Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diphenylbutylpiperidines also inhibit potassium-induced calcium-dependent contractions of rat vas deferens at concentrations of 40-350 nM. Other phenothiazine and butyrophenone neuroleptics lack such potent calcium-antagonist actions. Diphenylbutylpiperidines also differ from other neuroleptics in their ability to relieve negative symptoms of schizophrenia, such as emotional withdrawal, as well as the positive symptoms which respond to all neuroleptics. We suggest that these unique antischizophrenic actions are related to a blockade by diphenylbutylpiperidines of voltage-operated calcium channels.

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“…The pharmacological effects of 1,4-DHP calcium antagonists are due to an interaction with specific receptors in the cardiovascular system. The binding properties of calcium antagonists to these receptors were characterized extensively in vitro in brain, myocardial, and smooth muscles (Bellemann et al, 1981;Bolger et al, 1982;Ehlert et al, 1982;Gould et al, 1982;Godfraind et al, 1986). However, the in vitro receptor affinities of calcium antagonists may not reflect the pharmacological activity and the tissue selectivity in vivo of these drugs because the in vitro binding technique does not take various pharmacokinetic (absorption, distribution, elimination) and pharmacodynamic factors into account.…”

Section: Introductionmentioning

confidence: 99%

The receptor occupation and plasma concentration of NKY‐722, a water‐soluble dihydropyridine‐type calcium antagonist, in spontaneously hypertensive rats

Uchida

Yamada

Ohkura

et al. 1995

British J Pharmacology

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The occupation in vivo by NKY‐722 of 1,4‐dihydropyridine (DHP) calcium antagonist receptors in myocardium, aorta and cerebral cortex was investigated. At 1 and 3 h after oral administration of NKY‐722 (3 mg kg−1) in spontaneously hypertensive rats (SHR), there was a significant (44 and 41%, respectively) decrease in the number of myocardial (+)‐[3H]‐PN 200‐110 binding sites (Bmax) compared to control values. A greater reduction of Bmax values was observed at 1 (86%), 3 (88%), 6 (63%) and 12 (46%) h later by a higher dose (10 mg kg−1) of this drug. The occupation of myocardial 1,4‐DHP calcium antagonist receptors after oral administration of NKY‐722 correlated significantly with its plasma concentration. There was a significant decrease in cerebral cortical (+)‐[3H]‐PN 200‐110 binding (Bmax) at 1 and 3 h after oral administration of NKY‐722 (10 mg kg−1). Oral administration of nicardipine (10 mg kg−1) in SHR caused a significant reduction of Bmax values for (+)‐[3H]‐PN 200‐110 binding in myocardium at 1 and 3 h later and in cerebral cortex at 1 h later. The in vivo specific binding of (+)‐[3H]‐PN 200‐110 in particulate fractions of aorta of SHR was significantly (79 and 83%, respectively) reduced at 1 and 6 h after oral administration of NKY‐722 (3 mg kg−1), while myocardial (+)‐[3H]‐PN 200‐110 binding was decreased by 52% only at 1 h later. Also, nicardipine administration reduced in vivo (+)‐[3H]‐PN 200‐110 binding in aorta at 1 and 6 h later and in myocardium at 1 h later. On the other hand, the administration of both NKY‐722 and nicardipine had no significant effect on in vivo (+)‐[3H]‐PN 200‐110 binding in cerebreal cortex. It is concluded that NKY‐722 may exert more selective and sustained occupation in vivo of 1,4‐DHP calcium antagonist receptors in vascular tissues of SHR than in myocardial and brain tissues.

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The binding of [3H]nitrendipine to receptors for calcium channel antagonists in the heart, cerebral cortex, and ileum of rats

Cited by 230 publications

References 9 publications

Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain

Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.

The receptor occupation and plasma concentration of NKY‐722, a water‐soluble dihydropyridine‐type calcium antagonist, in spontaneously hypertensive rats

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