Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Membrane vesicles can be prepared from murine lymphoid cells by nitrogen cavitation and fractionated by sedimentation through nonlinear sucrose density gradients. Two subpopulations of membrane vesicles, PMI and PMII, can be distinguished on the basis of sedimentation rate. The subcellular distribution of adenylate and guanylate cyclases in these membrane subpopulations have been compared with the distribution of a number of marker enzymes. Approximately 20-30% of the total adenylate and guanylate cyclase activity is located at the top of the sucrose gradient (soluble enzyme), the remainder of the activity being distributed in the PMI and PMII fractions (membrane-bound enzyme). More than 90% of the 5'-nucleotidase and NADH oxidase activities detected in lymphoid cell homogenates are located in PMI and PMII fractions, whereas succinate cytochrome c reductase activity is detected only in the PMII fractions. In addition, beta-galactosidase activity is distributed in the soluble and PMII fractions of the sucrose density gradients. On the basis of the fractionation patterns of these various enzyme activities, it appears that PMI fractions contain vesicles of plasma membrane and endoplasmic reticulum, whereas PMII fractions contain mitochondria, lysomes, and plasma membrane vesicles. Approximately 30-40% of the adenylate and guanylate cyclase activities in PMII can be converted to a PMI-like form following dialysis and resedimentation through a second nonlinear sucrose gradient. Adenylate and guanulate cyclases can be distinguished on the basis of sensitivity to nonionic detergents.
 ...
PMID:The subcellular distribution of adenylate and guanylate cyclases in murine lymphoid cells. 0 90

Effects of peripheral benzodiazepine receptor modulating drugs, Ro 5-4864 and PK 11195, on tension induced by K+ and the calcium agonist SDZ 202 791 (S isomer), were studied in rat caudal arteries. A significant reduction of tonic phase tension occurred with 30 nM PK 11195 or 3 microM Ro 5-4864, but decreases of the initial (first 3 min), phasic contraction were detected only at the highest concentrations of Ro 5-4864 and PK 11195. Protoporphyrin IX, the putative endogenous ligand of the peripheral benzodiazepine receptor, (at 10-100 nM) markedly increased the effectiveness of Ro 5-4864 and PK 11195 in reducing phasic contraction. Intracellular calcium localization and distribution in fura-2 loaded single vascular cells were quantitated using a high sensitivity, two-stage microchannel plate, photon-counting (PMI-VIM) camera. Peripheral benzodiazepines reduced intracellular calcium release from centrally located calcium pools, and this decrease of calcium release was potentiated by protoporphyrin IX. The decrease in intracellular calcium activity, which was more pronounced in the central regions where sarcoplasmic reticular elements are numerous, was probably the major mechanism of these vasodilator properties. Measurements of soluble guanylate cyclase activity also supported the intracellular Ca2+ release mechanism. Under conditions where protoporphyrin IX did not significantly stimulate guanylate cyclase, Ro 5-4864 alone or more effectively in combination with protoporphyrin IX stimulated cGMP production and caused relaxation. Guanylate cyclase forms a possible target for these benzodiazepine modulators, a hypothesis that merits further investigation.
 ...
PMID:Relaxation of rat vascular muscle by peripheral benzodiazepine modulators. 256 75