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

Adenylate cyclase activity was measured in broken cell preparations of whole endometrial tissue from rabbits on Days 0, 1, 6.5, 9 and 15 of pseudopregnancy and in endometrial epithelial and stromal cells on Days 1 and 6.5 to assess the specific response of individual cell types. In dispersed cells, adenylate cyclase activity was higher (P less than 0.01) in stromal than in epithelial cells and reduced on Day 6.5 compared to Day 1 in both cell types. The response of adenylate cyclase to isoproterenol appeared more important relative to the PGE-2 response in epithelial than in stromal cells and strongly reduced in the former on Day 6.5. In endometrium, the overall adenylate cyclase activity was increased significantly on Day 1 of pseudopregnancy compared to Day 0 (oestrus), only 18 h after injection of hCG. On the following days, the activity decreased progressively on Days 6.5 and 9 and exhibited a recovery on Day 15. Adenylate cyclase response to isoproterenol (% over GTP) was comparable on Days 0, 1 and 6.5, abolished on Day 9 and recovered on Day 15. Maximal response to PGE-2 (% over GTP) was observed on Day 6.5, at the time of implantation, maintained on Day 9 and reduced on Day 15 towards the low levels measured in oestrus and Day 1 of pseudopregnancy. Our results demonstrate a dramatic alteration of adenylate cyclase activity in rabbit endometrium during pseudopregnancy. It suggests a possible involvement of catecholamines and prostaglandin E-2 in the regulation of endometrial receptivity through a cAMP-mediated process.
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PMID:Regulation of adenylate cyclase activity and stimulation response in relation to endometrial receptivity in the rabbit. 270 85

Parathyroid hormone (PTH) functions in part by regulating osteoblast cytokine expression. We recently demonstrated that PTH induced a rapid and transient increase in interleukin-6 (IL-6) mRNA expression in rat bones in vivo. To determine the molecular basis of this effect, we analyzed the human IL-6 promoter fused (-1,179 to +9) with the chloramphenicol acetyltransferase (CAT) reporter gene in stable transfections into human osteoblast-like osteosarcoma SaOS-2 cells. We compared the effects of PTH on IL-6 expression with adenylate cyclase activator forskolin, PKC activator phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, interleukin-1 alpha (IL-1 alpha), prostaglandin E-2 (PGE-2), RS-66271 (a parathyroid hormone-related peptide analog), and platelet-derived growth factor-BB (PDGF-BB). Analyses of cell clones showed that IL-6 promoter expression was extremely low in the unstimulated state. Exposure to PTH (0.001-100 nM) for 12 h stimulated CAT expression in a dose-dependent manner (200-500% of control). Treatment with IL-1 alpha was more potent than PTH in inducing transcription of the IL-6 promoter (900-1,000%). Activation of the cAMP-PKA pathway by treatment with forskolin induced a comparable level of induction with PTH. Together, the effects of PTH and forskolin were additive. RS-66271, previously shown to have PTH-like effects, induced a comparable level of IL-6 promoter expression. When examined together, PTH+RS-66271 effects were comparable to PTH effects alone. Exposure to PGE-2, PMA, PDGF-BB, or A23187 for 12 h did not significantly alter IL-6 promoter expression. These results demonstrate PTH, forskolin, the PTHrP analog RS-66271, and IL-1 alpha stimulate IL-6 expression by stimulating gene transcription. The response to forskolin suggests that the messenger system mediated by PKA is sufficient to induce IL-6 expression.
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PMID:Parathyroid hormone (1-34)-mediated interleukin-6 induction. 932 32

By examining in vitro the effects of prostaglandin E-2 (PGE-2) and prostaglandin F-2alpha (PGF-2alpha) induced in the corpora lutea (CL) of pseudopregnant rabbits, we have demonstrated that these prostaglandins modulate luteal nitric oxide synthase (NOS) activity and progesterone production differently, depending on the age of the CL. On CL obtained on day 4 of pseudopregnancy (day-4), PGE-2 was found to depress NOS total activity to 13% of control and to significantly increase basal progesterone secretion by 61%, while PGF-2alpha had no effect. On day-9 CL, PGE-2 was ineffective, but PGF-2alpha caused a 2.5-fold increase of NOS activity and a marked decrease in progesterone production. Using specific inhibitors, we found that the regulatory actions of PGE-2 in vitro are mediated via the adenyl cyclase/protein kinase A (PKA) second messenger system, while the PGF-2alpha-induced luteolytic effects on day-9 CL depend upon activation of the phospholipase C/protein kinase C (PKC) system. The different responsiveness of day-4 and day-9 CL to PGE-2 and PGF-2alpha could depend on receptor availability for these two prostaglandins, even if other cellular mechanisms cannot be excluded. The present study supports a functional role for NOS in regulating the steroidogenic capacity of rabbit CL, and reveals a novel interaction between a stimulatory G-protein-coupled receptor and PKC/PKA-mediated signal transduction modulating NOS activity.
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PMID:Nitric oxide synthase activity and progesterone release by isolated corpora lutea of rabbits in the early and mid-luteal phases of pseudopregnancy are modulated differently by prostaglandin E-2 and prostaglandin F-2alpha via adenylate cyclase and phospholipase C. 1065 53