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)

Effects of the calcium antagonist verapamil on the synthesis of fetal rat bone collagen and noncollagen protein were investigated in tissue culture. Protein synthesis was quantitated by measuring the incorporation of [3H]proline into collagenase-digestible (CDP) and noncollagen protein (NCP) using bacterial collagenase; [3H]proline was added for the last 2 h of culture. Verapamil (10(-5)--10(-4) M) decreased the incorporation of label into CDP and NCP after 24 h of culture; CDP formation was inhibited to a greater extent than NCP. The inhibitory response was observed in the presence and absence of unlabeled medium proline and was not associated with changes in trichloroacetic acid-extractable radioactivity. Increasing medium calcium from 1.0 to 5.0 mM did not affect the response to 10(-4) M verapamil, whereas 3.0 mM calcium abolished the response to 10(-5) M verapamil. The inhibitory effect was reversed by 48 h of control treatment subsequent to 24-h treatment with the antagonist. Verapamil did not decrease the incorporation of [3H]thymidine into DNA or [3H]uridine into RNA, nor was there any effect of the antagonist on the DNA content of cultured bones. The prostaglandin synthetase inhibitor indomethacin did not affect the response to verapamil. We conclude that a critical concentration of intracellular calcium is necessary for normal synthesis of skeletal protein in tissue culture, and that collagen may be more sensitive to changes in intracellular calcium than NCP. In addition, other ions (e.g. sodium and potassium) may also be involved in the control of skeletal protein synthesis.
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PMID:Effects of the calcium antagonist verapamil on in vitro synthesis of skeletal collagen and noncollagen protein. 48 4

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

The involvement of the calcium messenger system in the control of steroidogenesis in the rat and bovine adrenal cortex has been studied extensively. However the role of these second messengers in the control of human adrenocortical function is not established. This was therefore studied by incubating collagenase-dispersed human adrenocortical cells with the calcium ionophore A23187 and the protein kinase C activator phorbol 12-myristate 13-acetate (TPA). The effects of the calcium channel blocker verapamil on basal and stimulated steroidogenesis were also studied. Both TPA (1 pmol/l-10 mumol/l) and A23187 (1 nmol/l-10 mumol/l) caused a dose-dependent increase in cortisol, aldosterone and corticosterone production. Verapamil (10 mumol/l) inhibited the increase in aldosterone, corticosterone and cortisol produced in response to ACTH(1-24), potassium, and desacetyl-alpha MSH. Unlike previous results in the rat, these effects were not specific for aldosterone secretion. The results suggest that, as in other species, calcium mobilization and protein kinase C activation have a role in the control of steroidogenesis in the human adrenal cortex. However, in contrast to the rat, these mechanisms appear to be involved in the control of steroidogenesis in both the zona glomerulosa and inner zone cells.
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PMID:Control of steroidogenesis by the calcium messenger system in human adrenocortical cells. 201 56

Cytoplasmic Ca2+ is regarded as an intracellular messenger for acetylcholine- and cholecystokinin (CCK)-stimulated pancreatic enzyme secretion. We investigated in the in vitro model of isolated rat pancreatic acini whether or not Ca2+-channel blockers are able to inhibit Ca2+-mediated enzyme secretion. Isolated rat pancreatic acini were prepared via collagenase digestion. The effect of various Ca2+-channel blockers on amylase secretion stimulated by various secretagogues was monitored. Verapamil, but not nitrendipine, dose-dependently reduced CCK8- and carbachol-stimulated enzyme secretion. Higher doses of either CCK8 or carbachol could not reverse the inhibition caused by verapamil. Amylase secretion stimulated by the ionophore A23817 was not altered by verapamil. Verapamil augmented enzyme secretion stimulated by secretagogues which work through cAMP as second messenger. 3H-N-methylscopolamine- and 125I-Bolton-Hunter-CCK8-binding to pancreatic acini was dose-dependently inhibited by verapamil, but the inhibition curves did not parallel the inhibition curves with unlabeled receptor agonists. Thus, the impairment of exocrine pancreatic amylase secretion by verapamil is probably not due to its known "Ca2+-channel" blocking abilities in other tissues but is rather caused by noncompetitive effects on the level of muscarinic receptors and receptors for CCK.
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PMID:Influence of "calcium2+-channel blockers" on exocrine pancreatic secretion by isolated rat acini. 246 43

Recent data have implicated the phosphatidylinositol/calcium second-messenger system in the control of aldosterone secretion by the adrenal zona glomerulosa. However, in the rat adrenal there are few reports of a direct effect of protein kinase C activation on steroid secretion, while the effects of calcium mobilization may be variable. Since the rat adrenal zona glomerulosa is sensitive to the mode of tissue preparation, these mechanisms were reinvestigated in intact (non-dispersed) capsular tissue and collagenase-dispersed zona glomerulosa cells. Steroidogenesis in the intact zona glomerulosa was markedly affected by agonists of the calcium messenger system. Most notably, aldosterone and 18-hydroxycorticosterone (18-OH-B) secretion were stimulated by A23187 (100 nmol to 10 mumols/l) and BAY K 8644 (500 nmol/l). Phorbol 12-myristate 13-acetate (TPA; 1 pmol to 1 mumol/l) stimulated aldosterone secretion at all doses and caused a dose-dependent increase in 18-OH-B and 18-hydroxydeoxycorticosterone (18-OH-DOC) secretion. Corticosterone secretion was slightly increased in the presence of A23187 but not by TPA or BAY K 8644. Production of 18-OH-DOC was unaffected by A23187 and BAY K 8644. The calcium channel antagonist verapamil (10 mumols/l) inhibited ACTH-stimulated aldosterone secretion by the intact zona glomerulosa but had no effect on corticosterone secretion. Verapamil (10 mumols/l) also inhibited the increase in aldosterone secretion by collagenase-dispersed zona glomerulosa cells stimulated by ACTH (100 fmol to 100 nmol/l), angiotensin II (100 pmol to 10 nmol/l) and potassium (5.9 and 8.4 mmol/l); stimulated corticosterone secretion was unaffected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Specific effects of agonists of the calcium messenger system on secretion of 'late-pathway' steroid products by intact tissue and dispersed cells of the rat adrenal zona glomerulosa. 247 55

We previously reported that thyrotropin-releasing hormone (TRH) and human pancreatic growth hormone-releasing factor (hpGRF) exert synergistic (greater than additive) effects on growth hormone (GH) release from chicken pituitary cells in primary culture. In the present studies the possible participation of calcium in GH release and in TRH and hpGRF synergy was investigated. Following dispersion with collagenase, cells were cultured for 48 hr prior to exposure (2 hr) to test agents. Cultured cells were exposed to a range of calcium concentrations (0, 0.02, 0.2, and 2.0 mM) in the presence and absence of secretagogues. These results demonstrated that basal GH release was not altered by the concentration of calcium in the medium: however, secretagogue-induced GH release required calcium. Thus, TRH, hpGRF, 8 Br-cAMP, or forskolin stimulated GH release in the absence of calcium. Furthermore, synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, or forskolin was observed only at the highest calcium concentration (2.0 mM). In other studies, ionomycin (10(-5) M), a calcium ionophore, stimulated GH release to a value about 125% over the basal (absence of test agent) value. Ionomycin-induced GH release was not affected by TRH (5.0 ng/ml); the combined effects of ionomycin (10(-7)-10(-5) M) and hpGRF (5.0 ng/ml) on GH release were less than additive. However, ionomycin (10(-5) M) further increased GH release over that resulting from the synergistic action of TRH and hpGRF (5.0 ng/ml each). Verapamil (a calcium channel blocker) did not affect GH release induced by either TRH or hpGRF (5.0 ng/ml each). However, this agent did inhibit synergistic GH release evoked by TRH and hpGRF, 8 Br-cAMP, forskolin, or isobutylmethylxanthine. These results suggest that calcium participates in secretagogue-induced GH release from chicken somatotrophs in vitro.
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PMID:Possible participation of calcium in growth hormone release and in thyrotropin-releasing hormone and human pancreatic growth hormone-releasing factor synergy in a primary culture of chicken pituitary cells. 250 91

Influence of extracellular calcium on gonadotropin hormone-releasing hormone (GnRH)-stimulated gonadotropin hormone (GtH) release from a teleostean fish (Channa punctatus) pituitary was examined in vitro by preparing enzymatically dispersed pituitary cell incubation. Effect of Ca2+ on GnRH-augmented GtH release was evaluated with partially purified C. punctatus GnRH (cGnRH) and synthetic mammalian GnRH (mGnRH). Cells were dispersed by 0.3% collagenase plus 0.05% trypsin in culture medium and a high yield of viable cells were obtained. Addition of cGnRH (10 micrograms/ml) to pituitary cells in Ca2+-free medium resulted in a significant increase in GtH release, but the addition of Ca2+ (2 mM) enhanced it to about four- and threefold over cGnRH and mGnRH, respectively. Increasing concentrations of Ca2+ (0.1-2.0 mM/well) with fixed concentrations of GnRH (10 micrograms/ml) or increasing doses of GnRH (2.5 to 20 micrograms/ml) with fixed amount of Ca2+ (2 mM/well) resulted in a dose dependent increase in GtH release. EDTA or EGTA (2 mM/well) completely suppressed the Ca2+-augmenting effect of GnRH-stimulated GtH release. Addition of lanthanum (La3+, 4 mM/well), a competitive inhibitor of Ca2+, reduced 60% of the Ca2+ (2 mM/well) stimulation. Verapamil, a specific Ca2+ channel blocker, when added in increasing concentrations (1-100 microM/well) to pituitary cell incubations containing GnRH-stimulated GtH release in Ca2+-free medium could be waived by EGTA (2 mM/well), indicating availability of extracellular calcium from tissue sources. The uptake of radioactive Ca2+ by pituitary cells was greatly enhanced by GnRH while the addition of verapamil (10 microM/well) not only inhibited the GnRH-stimulated uptake, but also reduced it below the control level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Requirement of extracellular calcium in fish pituitary gonadotropin release by gonadotropin hormone-releasing hormone. 265 52

Seven patients with epidermolysis bullosa dystrophica and chronic and recurrent oesophageal lesions such as spasm, strictures, and complete occlusion were studied. Dysphagia could be cured with drugs if it was caused by bullae formation or spasm. If oesophageal strictures were present, endoscopy and bouginage with corticosteroid prophylaxis during the quiescent phase of the disease was a safe and useful procedure. We have also given corticosteroids, which reduced the oedema caused by bullae formation and oral phenytoin, which reduced epithelial detachment by inhibiting collagenase activity. Verapamil counteracted oesophageal spasm and pureed food during periods of dysphagia reduced blistering of the upper oesophagus.
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PMID:Management of oesophageal stenosis in epidermolysis bullosa dystrophica. 275 29

Calcium antagonist increase extracellular matrix collagenase activity as well as decrease collagen, fibronectin synthesis and secretion, altering fibroblastic metabolism. Preliminary findings reports that Verapamil improves would healing; Levine (1994) suggest that intralesional calcium antagonist (Verapamil) therapy offers an economical and sensible non operative approach for the treatment of Peyronie's disease. We studied and verified the effect of Verapamil in Peyronie's plaque on 39 men. They received injections of Verapamil bi-weekly in to the plaques for 6 months. Subjectively, improvement in rigidity was observed in 23,1% and a plaque softening observed in 48,7%. Rapid resolution of pain was verified in 90,9%. Objectively, curvature improved in 50% of those in which the diagnosis of Peyronie's disease was less than one year old, but in only 10.2% when disease lasted more than one year. A decreased plaque volume was not observed. There was no toxicity related to Verapamil effect. In this nonrandomized study we retained that Verapamil appears to result in an improvement in patients with symptoms lasting less than one year. For patients without pain with symptoms related to more than one year, Verapamil had no important effect.
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PMID:[Clinical effects of verapamil in the treatment of Peyronie's disease]. 892 94

Keloid scars are one of the most challenging problems for physicians and surgeons. These scars have been treated in many ways, with varying success. Verapamil is a widely used calcium channel antagonist, and it has been shown that calcium channel blockers inhibit the synthesis/secretion of extracellular matrix molecules, including collagen, glycosaminoglycans, and fibronectin, and increase collagenase. In this study, we performed total keloid excision in combination with reconstruction with W-plasty or skin grafting and injection of verapamil hydrochloride into the lesions of 21 patients with keloids. Patients were followed for minimum of 2 years, and the treatment outcome was evaluated based on the cosmetic appearances, symptomatic improvements, and the results of microscopic examinations. Also, patient satisfaction was scored with a visual analog scale. Two years after the operations, two patients had keloid in lesser diameter than the original lesions, two patients had lesions that were hypertrophic scars in appearance, and four patients had pruritus. One patient had keloid on the donor site. The rate of patient satisfaction was 6.4 on a scale of 1 to 10. We reviewed the treatment of keloid in this study and obtained one of the lower rates of complication in the literature. We believe that surgical excision with W-plasty or skin grafting and intralesional verapamil injection may be a good alternative in the treatment of keloid.
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PMID:Combination of surgery and intralesional verapamil injection in the treatment of the keloid. 1472 33


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