Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effect of diltiazem on glucose-induced insulin secretion was investigated in the rat islets of Langerhans isolated by a collagenase digestion technique. It was found that B-cells, main constituents of isolated islet preparations, had a well-preserved ultrastructural appearance immediately following isolation or after incubation with glucose or glucose and diltiazem. The islets released a large amount of insulin upon stimulation with glucose and CaCl2. Diltiazem (10(-6)-10(-4) M) produced a dose-related inhibition of glucose-induced insulin secretion and this effect was antagonized by the increase in extracellular concentration of CaCl2. The inhibitory effect of diltiazem on the insulin secretion was also counteracted by dibutyryl-3',5'-cyclic AMP or by theophylline. Among calcium-antagonists tested, nifedipine produced the most powerful inhibitory action on the insulin secretion, while the effect of verapamil was similar to or somewhat stronger than that of diltiazem. It was suggested that diltiazem may reduce the intracellular concentration of free calcium ion, thus causing an inhibitory effect on the glucose-induced insulin secretion by the isolated islets of Langerhans.
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PMID:Effect of diltiazem on insulin secretion. I. Experiments in vitro. 20 92

The effects of the calcium channel blockers, diltiazem and verapamil, on osteoblastic functions were investigated in cultured osteoblastic cells MC3T3-E1. DNA synthesis was evaluated by the incorporation of [3H]thymidine, and collagen synthesis by measuring the incorporation of [3H]proline into collagenase-digestible protein (CDP) and noncollagen protein (NCP). Diltiazem inhibited the DNA synthesis of osteoblastic cells by up to 57.6 and 54.6% at concentrations of 25 and 50 microM. Verapamil also significantly inhibited DNA synthesis by up to 61.6 and 40.9% at concentrations of 25 and 50 microM. The percent control of CDP formation were decreased by up to 76.7% in 5 microM and 44.3% in 50 microM of diltiazem. Verapamil also decreased CDP synthesis to 49.7% at 10 microM and 32.6% at 50 microM. NCP synthesis was decreased by the calcium channel blocker but inhibition of the CDP formation was greater than that of NCP. The calculated percent collagen synthesis was decreased at a calcium channel blocker concentration of 10 microM. The inhibitory effects of diltiazem and verapamil on percent collagen synthesis were not reversed by increasing the calcium concentration of culture media by either 1 or 5 mM. From this study, we conclude that calcium channel blockers have a direct inhibitory effect on osteoblastic function. Long-term administration of diltiazem or verapamil produces adverse effects on normal bone metabolism.
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PMID:Responses of osteoblastic cell line MC3T3-E1 cell to the calcium channel blocker diltiazem and verapamil. 166 33

1. The effect of the Ca2+-channel blocker diltiazem on hepatic apolipoprotein B (apo B) synthesis and secretion was studied in 12-18 h cultures of collagenase-dispersed rat hepatocytes. 2. The presence of diltiazem in the medium decreased apo B secretion by hepatocytes in a concentration-dependent manner. At 25 microM, diltiazem inhibited apo B secretion by approx. 36%, but there was no evidence of intracellular accumulation of apo B. 3. The inhibition of apo B secretion by hepatocytes was significantly correlated with cell-associated diltiazem (r = 0.72, P less than 0.01). 4. The rate of apo B secretion remained linear over 16 h even in the presence of 50 microM-diltiazem. 5. At diltiazem concentrations in the medium which were inhibitory for apo B secretion, [14C]acetate incorporation into cellular lipids and [35S]methionine incorporation into protein were enhanced. 6. Diltiazem inhibited the secretion of the apo B variants with a preferential inhibition of the higher-molecular-mass form of apo B (apo BH) over the lower-molecular-mass form (apo BL) at diltiazem concentrations in the medium greater than 25 microM. 7. Together, these results suggest that Ca2+ may play an important role in the synthesis and secretion of apo B-containing lipoproteins.
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PMID:Inhibition of apolipoprotein B net synthesis and secretion from cultured rat hepatocytes by the calcium-channel blocker diltiazem. 259 13

The influence of semotiadil fumarate, a novel vasoselective Ca2+ channel antagonist with a benzothiazine skeleton, was measured on the high-threshold Ca2+ current ICa,L in guinea-pig ventricular myocytes prepared by coronary perfusion with collagenase solution. Patch- and voltage-clamp methods were used to measure ICa,L. Diltiazem, nifedipine and amlodipine were studied for comparison. Samotiadil could be shown to inhibit ICa,L in a dose-dependent manner in concentrations similar to those of diltiazem but was less effective than amlodipine and nifedipine. The IC50 for nifedipine and amlodipine was in the range between 0.1 and 1 microM and that of semotiadil and diltiazem was between 10 and 100 microM. Recovery from inactivation of ICa,L in the control and under the influence of nifedipine 0.01 microM) and amlodipine (0.1 microM) was complete alter I. Semotiadil (0.1 microM) and diltiazem (1 microM) prolonged the time to full recovery to 20 s. This significant delay in the recovery of ICa,L produced by semotiadil indicates a mode of action similar to that of the verapamil type of Ca2+ channel antagonists and masses a clear distinction between it and the dihydropyridines, which have no effect on the recovery process. The rate dependence of the effect in combination with a distinct influence of the holding potential underlines the use dependence of the mechanism underlying the effect of semotiadil. The well-known high vasoselectivity of semotiadil in combination with a relatively low Ca2+ channel antagonistic influence on the heart makes semotiadil an interesting candidate for the treatment of coronary heart diseases.
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PMID:A novel benzothiazine Ca2+ channel antagonist, semotiadil, inhibits cardiac L-type Ca2+ currents. 909 94