inositol-1-4-5-trisphosphate and 6-anilino-5-8-quinolinedione

In this study, to investigate the role of inositol 1,4,5-trisphosphate (IP3) in nitric oxide-guanosine 3',5'-cyclic monophosphate (NO-cGMP)-induced isoflavone accumulation in soybean sprouts under UV-B radiation, the sprouts were treated with donors and inhibitors of NO and cGMP as well as IP3 inhibitor. Results showed that NO, with cGMP as a second messenger, stimulates IP3 accumulation under UV-B radiation. Consistent with the increase in IP3 content, the up-regulation of gene and protein expression of phosphoinositide-specific phospholipase C (PI-PLC) in response to sodium nitroprusside (SNP) (exogenous NO donor) and 8-Br-cGMP (cGMP analogue) was also observed. In addition, protein kinase G (PKG) participated in NO-cGMP-induced IP3 production. IP3 induced by the NO-cGMP pathway was involved in isoflavone synthesis by elevating the activity and gene and protein expressions of chalcone synthase (CHS) and isoflavone synthase (IFS). Overall, IP3 mediates NO-cGMP-induced isoflavone accumulation in soybean sprouts under UV-B stress.

Topics: Acyltransferases; Aminoquinolines; Carbazoles; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Glycine max; Inositol 1,4,5-Trisphosphate; Isoflavones; Nitric Oxide; Nitroprusside; Plant Proteins; Seedlings; Ultraviolet Rays

Topics: Adenosine Diphosphate Ribose; Aminoquinolines; Animals; Calcimycin; Calcium Signaling; Cyclic ADP-Ribose; Cyclic GMP; Enzyme Inhibitors; Female; Fertilization; Guanylate Cyclase; Inositol 1,4,5-Trisphosphate; Ionophores; Male; Models, Biological; Nitric Oxide; Oocytes; Ryanodine Receptor Calcium Release Channel; Sea Urchins; Seawater; Zygote

The effects of nitric oxide on the activities of thapsigargin-sensitive sarcoplasmic reticulum Ca2+-ATPase (SERCA) and Ca2+ uptake by sarcoplasmic reticulum (SR) membranes prepared from white skeletal muscle of rabbit femoral muscle were studied. Pretreatment of the SR preparations with nitric oxide at concentrations of up to 250 microM for 1 min decreased the SERCA activity concentration dependently, and also decreased their Ca2+ uptake. Both these effects of nitric oxide were reversible. Inhibitors of guanylyl cyclase and protein kinase G (PKG) had no significant effect on the nitric oxide-induced inhibitions of SERCA and Ca2+ uptake. Moreover, dithiothreitol did not reverse the inhibitory effects of nitric oxide on SERCA and Ca2+ uptake. These findings suggest that nitric oxide inhibits SERCA, mainly SERCA 1, of rabbit femoral skeletal muscle by an action independent of the cyclic GMP-PKG system or oxidation of thiols, and probably by a direct action on SERCA protein.

Topics: Aminoquinolines; Animals; Caffeine; Calcium; Calcium Channel Agonists; Calcium Channel Blockers; Calcium-Transporting ATPases; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Dithiothreitol; Guanylate Cyclase; Heparin; Inositol 1,4,5-Trisphosphate; Nitric Oxide; Ouabain; Rabbits; Ryanodine; Sarcoplasmic Reticulum; Sodium-Potassium-Exchanging ATPase; Thapsigargin; Thionucleotides

To investigate the effects of C-type natriuretic peptide (CNP) and sodium nitroprusside (SNP) on cyclic guanosine monophosphate (cGMP) accumulation and on carbachol (CCh)-stimulated inositol 1,4,5-triphosphate (IP3) production and contraction in ciliary muscle (CM) and iris sphincter (Sph) isolated from bovine and other mammalian species.. Ciliary muscle and sphincter isolated from cows, cats, dogs, rabbits, monkeys, and humans were used. Bovine specimens were used in the present work. Accumulation of cGMP and cyclic adenosine monophosphate (cAMP) in tissue extracts was measured by radioimmunoassay, IP3 production was measured by ion-exchange chromatography, and changes in tension were recorded isometrically.. In general, CNP and SNP exerted differential inhibitory effects on muscarinic-receptor-induced responses in CM and Sph isolated from the various species. Thus in bovine CM, SNP stimulated cGMP formation in a time- and concentration-dependent manner and dose dependently inhibited CCh-induced IP3 production and contraction. These effects were inhibited by LY 83583, a soluble guanylyl cyclase inhibitor, and mimicked by 8-Br-cGMP, a cell-membrane permeable analogue of cGMP. The inhibitory effects of the soluble cGMP analogue are tissue and species specific. Sodium nitroprusside had no effect on the muscarinic responses in bovine Sph, but it attenuated CCh-induced contractions in Sph isolated from cats, dogs, and rabbits. In bovine Sph, CNP increased cGMP accumulation in a time- and dose-dependent manner and dose dependently inhibited CCh-induced IP3 production and contraction. LY 83583 had no effect on the muscarinic responses. C-type natriuretic peptide attenuated CCh-induced contraction in CM isolated from monkey and human, but it had no influence on this response in CM isolated from cows, cats, and dogs.. In bovine CM, SNP effects are probably mediated through soluble guanylyl cyclase, whereas in Sph the CNP effects are mediated through membrane-bound guanylyl cyclase, which is associated with the type-B natriuretic peptide receptor. Agents that strongly increase intracellular cGMP levels, including SNP and CNP, produce significant inhibition of CCh-induced IP3 production and contraction. These effects are tissue and species specific. The results indicate that the cGMP signaling system, similar to the cAMP system, has a major inhibitory influence on the muscarinic responses in smooth muscles of the iris-ciliary body. The agents CNP and SNP, which stimulate cGMP accumulation in the ocular smooth muscles, could reduce intraocular pressure, presumably by increasing uveoscleral outflow induced by relaxation of the CM. However, the relationships between the CNP- and SNP-induced inhibition of the muscarinic stimulation and the reported intraocular pressure-lowering effects of the cGMP-elevating agents remain to be determined.

Topics: Aminoquinolines; Animals; Atrial Natriuretic Factor; Carbachol; Cats; Cattle; Ciliary Body; Cyclic AMP; Cyclic GMP; Dogs; Dose-Response Relationship, Drug; Guanylate Cyclase; Humans; Inositol 1,4,5-Trisphosphate; Iris; Macaca mulatta; Muscarinic Agonists; Muscle Contraction; Muscle, Smooth; Natriuretic Peptide, C-Type; Nitroprusside; Proteins; Rabbits; Radioimmunoassay

In the pancreatic acinar cell, hormonal stimulation causes a rise in the intracellular free Ca2+ concentration by activating the inositol 1,4,5-trisphosphate-mediated release of Ca2+ from intracellular stores (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205). The released Ca2+ is, for the most part, extruded from the cell, necessitating a mechanism for Ca2+ entry and reloading of intracellular Ca2+ stores (Putney, J. W., Jr. (1990) Cell Calcium 11, 611-624; Rink, T. J. (1990) FEBS Lett. 268, 381-385). However, neither the mechanism of depletion-activated Ca2+ entry nor the signal that activates it is known. We report here that a sustained inward current of depletion-activated Ca2+ entry can be measured in pancreatic acinar cells using patch-clamp recording methods. Furthermore, the current can be blocked by an inhibitor of guanylyl cyclase, can be reactivated by 8-bromo-cGMP after inhibition, and can be activated in the absence of Ca2+ depletion by perfusing the cell with cGMP, but not cAMP. Intracellular perfusion with 1,3,4,5-inositol tetrakisphosphate did not activate an inward current, whereas perfusion with 2,4,5-inositol trisphosphate did activate an inward current. We conclude that cGMP may be an intracellular messenger that regulates depletion-activated Ca2+ entry.

Topics: Aminoquinolines; Animals; Calcium; Calcium Channels; Cyclic AMP; Cyclic GMP; Guanylate Cyclase; In Vitro Techniques; Inositol 1,4,5-Trisphosphate; Inositol Phosphates; Kinetics; Membrane Potentials; Models, Biological; Pancreas; Rats; Rats, Sprague-Dawley; Second Messenger Systems; Time Factors