scispace - formally typeset
Search or ask a question
Topic

Cyclase

About: Cyclase is a research topic. Over the lifetime, 10162 publications have been published within this topic receiving 388566 citations.


Papers
More filters
Journal ArticleDOI
TL;DR: The data suggest that EDRF, produced spontaneously or in response to vasoactive agents, elevates endothelial cyclic GMP content by stimulating soluble guanylate cyclase, and is possible that this may serve as a feedback loop by which the endothelial cell modulates EDRf production.
Abstract: 1. Two directly-acting stimulants of soluble guanylate cyclase, glyceryl trinitrate (0.1 microM) and sodium azide (10 microM), and a receptor-mediated stimulant of particulate guanylate cyclase, atriopeptin II (10 nM), each elevated the cyclic GMP content of primary cultures of pig aortic endothelial cells without affecting the cyclic AMP content. 2. Two receptor-mediated stimulants of adenylate cyclase, glucagon (1 microM) and isoprenaline (10 microM), had no effect on the cyclic AMP or cyclic GMP content of these cells, but the directly acting stimulant, forskolin (30 microM), induced a small increase in cyclic AMP content. 3. Three agents that release endothelium-derived relaxing factor (EDRF); bradykinin (0.1 microM), ATP (10 microM) and ionophore A23187 (0.1 microM), each markedly elevated the cyclic GMP content of pig aortic endothelial cells, but acetylcholine (1 microM) had no effect. None of these agents had any effect on cyclic AMP content. 4. Two agents that potentiate the actions of EDRF; M & B 22948 (100 microM) and superoxide dismutase (30 units ml-1), each elevated the cyclic GMP content of pig aortic endothelial cells without affecting the cyclic AMP content. Pretreating cells with catalase (100 units ml-1) did not affect the rise in cyclic GMP content induced by superoxide dismutase (30 units ml-1). 5. Pretreatment of pig aortic endothelial cells with haemoglobin (10 microM) reduced the resting content of cyclic GMP and blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 microM), sodium azide (10 microM), bradykinin (0.1 microM), ATP (10 microM), ionophore A23187 (0.1 microM), M & B 22948 (100 microM) and superoxide dismutase (30 units ml-1), but not that induced by atriopeptin II (10 nM). 6. Pretreatment of pig aortic endothelial cells with an inhibitor of soluble guanylate cyclase, methylene blue (20 microM), had no effect on the resting content of cyclic GMP. Methylene blue (20 microM) blocked the increase in cyclic GMP content induced by glyceryl trinitrate (0.1 microM), M & B22948 (100 microM) and bradykinin (0.1 microM), but not that induced by atriopeptin II (10 nM). 7. The data show that soluble guanylate cyclase, particulate guanylate cyclase and adenylate cyclase are present in pig aortic endothelial cells. They further suggest that EDRF, produced spontaneously or in response to vasoactive agents, elevates endothelial cyclic GMP content by stimulating soluble guanylate cyclase. It is possible that this may serve as a feedback loop by which the endothelial cell modulates EDRF production.

124 citations

Journal ArticleDOI
TL;DR: A selective decrease in the beta 1-subtype of adrenergic receptors and an increase in a 40-kd G1-like protein in the failing heart are demonstrated.
Abstract: Changes in the beta-adrenergic receptor-G protein-adenylate cyclase complex were investigated in an experimental canine model of low-output heart failure produced by chronic rapid ventricular pacing. The contractile response occurring after exposure to the beta-adrenergic agonist dobutamine, measured as peak left ventricular + dP/dt, was decreased after 3 weeks of pacing. To further characterize the diminished functional responsiveness to beta-adrenergic receptor stimulation, beta-adrenergic receptor-adenylate cyclase coupling was investigated using membranes prepared from both control and paced animals. The density of beta-adrenergic receptors was decreased by 40% with a selective downregulation of the beta 1-subtype. The affinity of the receptor for the antagonist radioligand [125I]iodocyanopindolol remained unchanged. A defect in coupling was suggested by a decreased ability of isoproterenol, fluoride, and forskolin to stimulate adenylate cyclase in membranes prepared from failing hearts. Determination of the levels of Gi alpha (the alpha-subunit of Gi) by immunoblotting and pertussis toxin labeling revealed modest increases of approximately 30%. Furthermore, Mn2+ and purified Gs failed to stimulate adenylate cyclase in membranes prepared from failing hearts, indicating an impairment in the catalytic moiety of adenylate cyclase itself or in the ability of adenylate cyclase to couple to Gs. In contrast, complementation assay did not reveal differences in the functional activity of Gs alpha (the alpha-subunit of Gs). Taken together, these data demonstrate a selective decrease in the beta 1-subtype of adrenergic receptors and an increase in a 40-kd G1-like protein in the failing heart. Similar changes have been described in human idiopathic dilated cardiomyopathy. In addition to these changes, we identified a possible defect at the level of the catalytic subunit of adenylate cyclase.

124 citations

Journal ArticleDOI
TL;DR: Electroelution of the 216-kDa band following sodium dodecyl sulfate-polyacrylamide gel electrophoresis yields a preparation with both AC enzyme and toxin activities, indicating that this protein represents the AC holotoxin molecule.

124 citations

Journal ArticleDOI
TL;DR: The data suggest that, under certain conditions, large increases in the intra-cellular concentration of cyclic AMP may not be necessary for stimulation ofalpha-amylase release by adrenergic agonists, and demonstrate the need for caution in interpreting evidence obtained using alpha-adrenergic blocking agents as tools for investigation of alpha- and beta- adrenergic antagonism.

124 citations

Journal ArticleDOI
TL;DR: This work characterized highly selective receptors for PACAP, the pituitary adenylate cyclase activating peptide, in the tumoral acinar cell line AR 4‐2J derived from the rat pancreas, and found their potency was much higher than that of VIP and helodemin.

123 citations


Network Information
Related Topics (5)
Receptor
159.3K papers, 8.2M citations
91% related
Protein kinase A
68.4K papers, 3.9M citations
90% related
Binding site
48.1K papers, 2.5M citations
88% related
Phosphorylation
69.3K papers, 3.8M citations
88% related
Mitochondrion
51.5K papers, 3M citations
87% related
Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202324
202257
202145
202048
201939
201856