Decreased lymphocyte blastogenesis, IL2 production and NK activity following nifedipine administration to healthy humans

Morgano, A.; Pierri, Ivana; Stagnaro, R.; Setti, Maurizio; Puppo, Francesco; Indiveri, F

doi:10.1007/bf00316092

Cited by 17 publications

(11 citation statements)

References 27 publications

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“…These were used at higher concentrations than required to block voltage‐gated Ca 2+ channels and at concentrations far higher than estimated therapeutic levels. Using l ‐type channel antagonists a number of studies showed profound effects on T‐ and B‐cell activation and AgR‐induced Ca 2+ influx 71–77 . Whilst these pharmacological studies provide some evidence for the expression of Ca 2+ channels related to voltage‐gated Ca 2+ channels, they should at the same time be treated with some caution due to the high concentrations of drugs used.…”

Section: Plasma Membrane Calcium Channelsmentioning

confidence: 99%

Calcium channels in lymphocytes

Grafton

Thwaite

2001

Immunology

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Section: Plasma Membrane Calcium Channelsmentioning

confidence: 99%

Calcium channels in lymphocytes

Grafton

Thwaite

2001

Immunology

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“…Besides, CCBs increase the serum level of CS-A by inhibiting the cytochrome P-450 system in the liver, thus resulting in a decrement in the cost of the CS-A therapy. Furthermore CCBs have been reported to mediate an augmentation of the immunosuppressive effect [7, 8, 9]. Despite the beneficial effects of CS-A and CCB in combination, GH is the undesirable outcome of this treatment.…”

Section: Introductionmentioning

confidence: 99%

Relationship between Gingival Hyperplasia and Class II Histocompatibility Antigens in Renal Transplant Recipients

Türkmen

Ak²,

Furuncuoglu³

et al. 2000

Nephron

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Gingival hyperplasia, a well-known side effect of ciclosporin A (CS-A), is much more prominent when CS-A is used in combination with calcium channel blockers, especially dihydropyridines. On the other hand, it is interesting to note that this complication is not observed in all patients using this drug combination. This study was conducted in order to investigate the relationship (if any) between major histocompatibility complex antigens and gingival hyperplasia. Seventy-six renal transplantation patients were evaluated by an experienced dentist for gingival hyperplasia. The patients were then divided into two groups according to the presence (group 1, n = 18) or absence (group 2, n = 58) of gingival hyperplasia. There was no significant difference between the two groups regarding age, sex, transplant age, donor type, antihypertensive and immunosuppressive therapy protocols, and CS-A levels. HLA-DR2 antigen was present in 63% of the patients with gingival hyperplasia and in 34% of the patients without gingival hyperplasia. However, the HLA-DR1 antigen frequencies were found to be 11 and 22% in group 1 and group 2, respectively. In patients receiving nifedipine as an antihypertensive therapy, gingival hyperplasia developed more often than in patients receiving verapamil or diltiazem. As a result, in renal allograft recipients with HLA-DR1 antigen, gingival hyperplasia was seen less frequently than in HLA-DR2-positive patients. It is believed that the presence of these antigens regulates the response of the patients to either CS-A and/or calcium channel blockers.

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“…Initial evidence for the presence of L-type Ca 2ϩ channels in lymphocytes relied on pharmacological studies using antagonists of these channels. A number of studies showed effects of these antagonists on B and T cell activation (21)(22)(23)(24). However, the drugs were used at higher concentrations than those used to block authentic voltage-gated Ca 2ϩ channels.…”

mentioning

confidence: 99%

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

Stokes¹,

Gordon²,

Grafton

2004

Journal of Biological Chemistry

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In T lymphocytes, engagement of the antigen receptor leads to a biphasic Ca 2؉ flux consisting of a mobilization of Ca 2؉ from intracellular stores followed by a lower but sustained elevation that is dependent on extracellular Ca 2؉ . The prolonged Ca 2؉ flux is required for activation of transcription factors and for subsequent activation of the T cell. Ca 2؉ influx requires as yet unidentified Ca 2؉ channels, which potentially play a role in T cell activation. Here we present evidence that human T cells express a non-voltage-gated Ca 2؉ channel related to L-type voltage-gated Ca 2؉ channels. Drugs that block classical L-type channels inhibited the initial phase of the antigen receptor-induced Ca 2؉ flux and could also inhibit the sustained phase of the Ca 2؉ signal suggesting a role for the L-type Ca 2؉ channel in antigen receptor signaling. T cells expressed transcripts for the ␣ 1 1.2 and ␣ 1 1.3 pore-forming subunits of L-type voltage-gated Ca 2؉ channels and transcripts for all four known ␤-subunits including several potential new splice variants. Jurkat T leukemia cells expressed a small amount of full-length ␣ 1 1.2 protein but the dominant form was a truncated protein identical in size to a truncated ␣ 1 1.2 protein known to be expressed in B lymphocytes. They further expressed a truncated form of the ␣ 1 1.3 subunit and auxiliary ␤1-and ␤3-subunit proteins. Our data strongly suggest that functional but non-voltage-gated L-type Ca 2؉ channels are expressed at the plasma membrane in T cells and play a role in the antigen receptor-mediated Ca 2؉ flux in these cells.

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Decreased lymphocyte blastogenesis, IL2 production and NK activity following nifedipine administration to healthy humans

Cited by 17 publications

References 27 publications

Calcium channels in lymphocytes

Calcium channels in lymphocytes

Relationship between Gingival Hyperplasia and Class II Histocompatibility Antigens in Renal Transplant Recipients

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

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