Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of several compounds acting through adenylate cyclase system and/or influencing prostaglandin biosynthesis on spermine-FBS cytotoxicity to human myelogenous leukemia K562 cells were studied. Salbutamol, a beta 2-adrenoceptor agonist inhibited to a certain extent spermine-FBS cytotoxic action to K562 cells, and propranolol, a beta 2-adrenoceptor antagonist, did not affect this inhibition. Aminophylline, an inhibitor of cyclic nucleotide phosphodiesterase, acted suppressing spermine-FBS cytotoxicity to K562 cells. Pretreatment of the cells with dexamethasone did not significantly alter salbutamol-related inhibition of spermine-FBS cytotoxicity. Indomethacin, an inhibitor of cyclooxygenases directly involved in prostaglandin biosynthesis, did not interfere with protective terbutaline effects against spermine-FBS cytotoxicity to K562 cells during the 24-hour period.
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PMID:To the mechanism of spermine-FBS cytotoxicity toward K562 human myelogenous leukemia cells. 820 12

The regulatory role of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) signaling has been implicated in embryonic skeletal development. Here, we studied chondrogenic differentiation of the mouse embryonal carcinoma-derived clonal cell line ATDC5 as a model of chondrogenesis in the early stages of endochondral bone development. ATDC5 cells retain the properties of chondroprogenitor cells, and rapidly proliferate in the presence of 5% FBS. Insulin (10 micrograms/ml) induced chondrogenic differentiation of the cells in a postconfluent phase through a cellular condensation process, resulting in the formation of cartilage nodules, as evidenced by expression of type II collagen and aggrecan genes. We found that differentiated cultures of ATDC5 cells abundantly expressed the high affinity receptor for PTH (Mr approximately 80 kD; Kd = 3.9 nM; 3.2 x 10(5) sites/cell). The receptors on differentiated cells were functionally active, as evidenced by a PTH-dependent activation of adenylate cyclase. Specific binding of PTH to cells markedly increased with the formation of cartilage nodules, while undifferentiated cells failed to show specific binding of PTH. Northern blot analysis indicated that expression of the PTH/PTHrP receptor gene became detectable at the early stage of chondrogenesis of ATDC5 cells, preceding induction of aggrecan gene expression. Expression of the PTH/PTHrP receptor gene was undetectable in undifferentiated cells. The level of PTH/PTHrP receptor mRNA was markedly elevated parallel to that of type II collagen mRNA. These lines of evidence suggest that the expression of functional PTH/PTHrP receptor is associated with the onset of chondrogenesis. In addition, activation of the receptor by exogenous PTH or PTHrP significantly interfered with cellular condensation and the subsequent formation of cartilage nodules, suggesting a novel site of PTHrP action.
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PMID:Chondrogenic differentiation of clonal mouse embryonic cell line ATDC5 in vitro: differentiation-dependent gene expression of parathyroid hormone (PTH)/PTH-related peptide receptor. 860 76

The levels of intracellular cAMP in human myometrial smooth muscle cells in serum-free medium, or medium that contained FBS (1%, vol/vol), were determined after treatment with the homologous peptides, calcitonin gene-related peptide (CGRP), adrenomedullin (ADM), and amylin, without or with added isobutylmethylxanthine (IBMX). These cells were sensitive to CGRP, responding in a dose-dependent manner, with maximal levels of cAMP being attained with 5 nM CGRP in the presence of IBMX (1 mM). In the absence of IBMX, the level of cAMP attained in cells treated with CGRP (5 nM) (675.3 +/- 58.8 pmol.mg protein.15 min; mean +/- SEM, n = 3) was approximately 90x that in nontreated cells (7.5 +/- 0.4 pmol.mg protein.15 min). The level of cAMP in myometrial cells treated with CGRP (5 nM)+IBMX (1 mM), 1998 +/- 420 pmol.mg protein.15 min, was 29x that in cells treated with IBMX alone (69.2 +/- 10.2). The maximum level of cAMP achieved by treatment with ADM+IBMX was similar to that with CGRP+IBMX, but the dose of ADM required (1 microM) was approximately 200x that of CGRP. Amylin amide also caused an increase in cAMP but with considerably less potency; at a concentration of 500 nM, amylin amide+IBMX effected a 2.3-fold increase in cAMP relative to IBMX alone. CGRP8-37, an antagonist of CGRP via the CGRP1 receptor, inhibited the action of CGRP, ADM, and amylin in myometrial cells. Treatment with [cys(ACM)2-7]-CGRP, a CGRP2 receptor agonist, did not cause an increase in the levels of cAMP in these cells. These findings are indicative that CGRP, ADM, and amylin act via that the CGRP1 receptor in human myometrial cells. Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypetide also caused a dose-dependent increase in cAMP in myometrial cells. The findings of this study are indicative that multiple neuropeptides, acting by way of heptahelical receptors linked to the G alpha s-subunit of the G-proteins, may contribute to the maintenance of uterine quiescence during some period of human pregnancy.
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PMID:Activation of adenylyl cyclase in human myometrial smooth muscle cells by neuropeptides. 928 49

Through selective activation of the gonadotropic signal transduction pathway, we have determined the probable site of the antigonadotropic effects of prostaglandin F2alpha (PGF2alpha) in the human granulosa-luteal cell (hGLC). The gonadotropic signal transduction pathway was activated at the level of the receptor (luteinizing hormone and beta-adrenergic), stimulatory G protein (Gs), adenylate cyclase (AC), and protein kinase A (PKA) by human chorionic gonadotropin (hCG) and isoproterenol (Iso), cholera toxin (CTX), forskolin, and dibutryl cAMP (Db cAMP), respectively. Concomitantly, the ability of PGF2alpha to inhibit progesterone production in response to the activation of this cascade at these different levels was examined. hGLCs were obtained from in vitro fertilization patients and were precultured for 8 d in Medium 199 supplemented with fetal bovine serum (M199; 10% FBS). Following the preculture period, cells were treated with either vehicle or one of the above activators of the gonadotropic pathway, either in the absence or presence of PGF2alpha (in M199; No FBS). Following the treatment period, media were collected and assayed for progesterone by RIA. Prostaglandin F2alpha (10(-6) M) significantly inhibited hCG (1 IU/mL), Iso (10(-5) M), CTX (1 microg/mL), and forskolin- (10(-5) M) stimulated progesterone production. Conversely, PGF2alpha did not inhibit progesterone production stimulated by a saturating concentration of Db cAMP (10(-6) M). The ability of PGF2alpha to inhibit hCG- or CTX-stimulated progesterone production was attenuated by pertussis toxin (PTX; 50 ng/mL). In conclusion, through a pertussis toxin-sensitive G protein, PGF2alpha inhibits progesterone production at a level below AC, and above the activation of PKA by cAMP.
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PMID:Stepwise activation of the gonadotropic signal transduction pathway, and the ability of prostaglandin F2alpha to inhibit this activated pathway. 974 35