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

Adenyl cyclase activity of rat pancreatic islet membrane was increased by secretin, pancreozymin, and isoproterenol, while ACTH, glucagon, growth hormone, and insulin had no effect. Both secretin and isoproterenol activations were enhanced by prostaglandin E1 (PGE1) and GTP. Isoproterenol activation was additive with PGE1, as was that of secretin with PGE1, but only in the presence of GTP. Secretin activation in the presence of PGE1 and GTP was equivalent to NaF stimulation. Kinetic analysis indicated that secretin and GTP increased the maximum velocity of the adenyl cyclase and tended to decrease the apparent affinity of the enzyme for ATP. Glucagon activation of islet membrane adenyl cyclase was dependent upon prior treatment of the membrane preparation with EGTA and the use of inhibitors of proteolytic enzymes during the collagenase digestion phase of islet preparation. These results suggest that hormonal regulation of insulin secretion may be affected by PGE1 and guanine nucleotide modulation of the adenyl cyclase activation process.
 ...
PMID:Hormonal regulation of pancreatic islet adenyl cyclase. 17 51

The effects of somatostatin on insulin release and cyclic AMP metabolism were studied in collagenase-isolated islets of Langerhans from the rat. Ceoncentrations from 500 to 2000 ng/ml significantly inhibited glucose stimulated insulin release, while 100 and 200 ng/ml were ineffective. Somatostatin (2000 ng/ml) inhibited insulin release and [3H]-cyclic AMP accumulation induced by 16.7 mM glucose after 10 and 30 min of incubation. In dose-response studies, the inhibition by somatostatin of the effect of glucose on [3H]cyclic AMP and insulin release could be overcome by a high concentration of the hexose (44.9 mM), suggesting competitive inhibition. In the absence of glucose, somatostatin inhibited [3H]cyclic AMP accumulation induced by the phosphodiesterase inhibitor, IBMX, while no inhibition was seen, again in the absence of hexose, when the [3H]cyclic AMP levels had been raised by the adenyl cyclase stimulator, cholera toxin. Somatostatin did not affect phosphodiesterase activity when added to islet homogenates, but preincubation of the islets with the peptide before homogenization decreased the activity by about 30%. It is suggested that somatostatin-induced inhibition of insulin release is, at least partially, mediated by cyclic AMP, probably through an action on islet adenyl cyclase.
 ...
PMID:Studies on the mechanisms of somatostatin action on insulin release. IV. effect of somatostatin on cyclic AMP levels and phosphodiesterase activity in isolated rat pancreatic islets. 19 42

Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor.
 ...
PMID:Gonadotropin receptors in experimentally induced ovarian tumors in mice. 19 83

Cartilage breakdown, as seen in inflammatory and degenerative joint diseases, can be mediated by proteolytic enzymes, such as the metalloproteinase collagenase, the only enzyme able to digest collagen at neutral pH. In vitro collagenase gene expression can be stimulated by the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. We have investigated the effect of prostaglandin E1 (PGE1) on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated collagenase mRNA levels in the rabbit synoviocyte cell line HIG-82. PGE1, but not PGE2 or PGF2 alpha, was able to selectively reduce collagenase mRNA levels in a dose-dependent fashion. PGE1 markedly increased intracellular levels of cAMP, while PGE2 and PGF2 alpha had little or no effect on cAMP production in the HIG-82 synoviocytes. Agents known to increase intracellular cAMP levels, such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), mimicked the effect of PGE1, on collagenase mRNA levels. PGE1, forskolin, and IBMX also decreased collagenase mRNA levels in human skin fibroblasts, demonstrating that this observation was not unique to the HIG-82 cell line. Transient transfection experiments carried out in HIG-82 cells using a 1.2-kilobase portion of the 5'-flanking region of the human collagenase gene linked to the reporter gene luciferase demonstrated that PGE1, forskolin, and IBMX exert their inhibitory effect on the promoter region of the collagenase gene.
 ...
PMID:Prostaglandin E1 inhibits collagenase gene expression in rabbit synoviocytes and human fibroblasts. 137 21

Medullary and cortical tubular cells were prepared from rat kidneys with collagenase treatment. Arginine vasopressin (AVP) stimulated cyclic AMP production both in medullary and cortical cells with a dose-response relationship at concentrations ranging from 10 microU/ml to 10 mU/ml, whereas parathyroid hormone (PTH) and calcitonin did only in the latter. Using this medullary cell system, effects of acute changes in endogenous plasma AVP levels in vivo on its cyclic AMP responsiveness to AVP (10 mU/ml) in vitro were examined. Acute elevation of plasma AVP levels induced by ip injection of 20% (w/v) polyethylene glycol-isotonic saline solution 3 h prior to sacrifice resulted in a 33% decrease in cyclic AMP responsiveness to AVP (desensitization). More prolonged elevation of plasma AVP levels by water restriction for 48 h, on the other hand, increased the responsiveness by 38 to 81%, which was restored to basal levels by ad libitum intake of water for another 48 h (positive feedback regulation). These maneuvers did not alter the cyclic AMP responsiveness to PTH (10 micrograms/ml) in cortical cells. The results suggest that AVP-stimulated adenyl cyclase in rat renal medulla may be regulated by changes in endogenous AVP levels even within the physiological range.
 ...
PMID:Altered cyclic AMP responsiveness to vasopressin in rat renal medullary dispersed cells by acute elevation of endogenous vasopressin. 629 51

Synovial fluid basic calcium phosphate (BCP) crystals are associated with severe destructive arthropathies characterised by synovial proliferation and non-inflammatory degradation of intra-articular collagenous structures. BCP crystals stimulate fibroblast and chondrocyte mitogenesis, metalloprotease secretion and prostaglandin production. As a tissue protective effect of prostaglandins has been suggested, we recently studied the effect of PGE1 on BCP crystal-induced mitogenesis and collagenase mRNA accumulation in human fibroblasts (HF). We demonstrated a dose-dependent inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation. The mechanism of PGE1 inhibition of BCP crystal-induced mitogenesis and collagenase mRNA accumulation was therefore explored. PGE1 (100 ng/ml) increased HF intracellular cAMP 40-fold over control. BCP alone caused no such change but inhibited the PGE1-induced increase in intracellular cAMP by at least 60%. The PGE1-induced increase in intracellular cAMP was also blocked by the adenyl cyclase inhibitor, 2',5'-dideoxyadenosine (ddA) (10 microM) and ddA reversed the PGE1-mediated inhibition of BCP crystal-induced mitogenesis. Dibutyryl cAMP also inhibited BCP crystal-induced mitogenesis in a concentration-dependent manner. Agents which increase intracellular cAMP levels such as the adenyl cyclase activator forskolin and the phosphodiesterase, inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effect of PGE1 on HF collagenase mRNA levels. PGE1 inhibits the biologic effects of BCP crystals through the cAMP signal transduction pathway and such inhibition may have significant therapeutic implications.
 ...
PMID:The role of cyclic-3',5'-adenosine monophosphate in prostaglandin-mediated inhibition of basic calcium phosphate crystal-induced mitogenesis and collagenase induction in cultured human fibroblasts. 751 87