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)

We elucidated the implication of oxygen radicals on airway hyperresponsiveness after ovalbumin (OA) challenge in guinea pigs. Ten days OA exposure increased airway responsiveness, i.e., a significant decrease in log [acetylcholine (Ach) PC200] (2.445 +/- 0.227) was observed compared with the control group (3.398 +/- 0.269). After OA exposure, the number of beta-adrenoceptors decreased by 38%, and adenylate cyclase activity decreased by 36% (isoproterenol stimulated) and 28% (basal). Significant increases in xanthine oxidase activities in lung tissue, bronchoalveolar lavage fluid (BALF), and serum were observed after the tenth OA exposure (49.1 +/- 11.7 mU/g tissue, 12.6 +/- 3.16 mU/ml, and 11.5 +/- 2.66 mU/ml, respectively) compared with those in the control group (7.35 +/- 6.48 mU/g tissue, 2.85 +/- 1.17 mU/ml, and 3.51 +/- 1.15 mU/ml, respectively). Administration of long-acting superoxide dismutase (SOD) (5,000 U/kg twice a day intraperitoneally) or gamma-glutamylcysteine ethyl ester (gamma-GCE) (10 mg/kg, twice a day, intraperitoneally), a prodrug of glutathione, maintained log [Ach PC200] (3.248 +/- 0.415 and 3.298 +/- 0.246, respectively) in spite of 10 days OA exposure. Decreases in the number of beta-adrenoceptors and adenylate cyclase activity were prevented by long-acting SOD or gamma-GCE. In contrast, long-acting SOD or gamma-GCE inhibited significantly, but not completely, the elevation of xanthine oxidase activities. These results support suggestions that oxygen radicals might be involved in the underlying mechanism of airway hyperresponsiveness after OA challenge in guinea pigs.
 ...
PMID:Implication of oxygen radicals on airway hyperresponsiveness after ovalbumin challenge in guinea pigs. 131 12

This study was designed to investigate the differential modulation of the L-type Ca2+ (ICa) and the delayed rectifier K+ (IK) currents by direct activation of adenylate cyclase in guinea pig ventricular preparations. Action potentials were measured with conventional microelectrodes in excised papillary muscles. Isoproterenol significantly shortened the action potential duration at 90% repolarization (APD90) at 0.1 nM but significantly prolonged it at a higher concentration (10 nM). A water-soluble forskolin derivative, 6-(3-dimethylaminopropionyl) forskolin (NKH-477), slightly but significantly shortened APD at 12 nM but not at a higher concentration (120 nM). Effects of isoproterenol and NKH-477 on ICa and IK were also investigated by use of the whole cell voltage-clamp technique in single ventricular cells. Isoproterenol increased not only IK but also ICa at the same threshold concentration (0.3 nM). In contrast, the threshold concentration of NKH-477 for increasing IK (approximately 1 nM) was clearly lower than that for increasing ICa (10 nM). These results indicate that ICa and IK channels could be differentially regulated during beta-adrenoceptor stimulation.
 ...
PMID:Differential modulation by adenylate cyclase of Ca2+ and delayed K+ current in ventricular myocytes. 818 33

NKH-477 is a water-soluble analogue of forskolin that stimulates adenylate cyclase and has antidepressant properties in the forced swim model of depression. The effect of chronic NKH-477 on locomotion and rearing and its behavioural interaction with lithium and inositol was tested. NKH-477 (1.5 mg/kg), administered acutely or chronically for 9 d to rats, induced a significant reduction in locomotor behaviour and rearing. In a second experiment, rats were pretreated with chronic dietary lithium, inositol or control diet for 3 wk before being injected with either saline or NKH-477. Inositol had no effect on the decreased locomotion and rearing induced by NKH-477. There was a significant, but transient, interaction between lithium and NKH-477 on rearing on the second and third days of treatment. The lithium group had lower baseline rearing than control or inositol-treated rats, and was not further affected by NKH-477 treatment. This is the first report of a marked effect of this forskolin analogue on locomotion and rearing, with no tolerance in the time frame examined. The interaction between NKH-477 and lithium suggests that the well-documented ability of lithium to inhibit stimulation of the cAMP system is relevant to its behavioural effects; however, the transient nature of this interaction, suggests that other biochemical mechanisms are involved in the behavioural effects of lithium.
 ...
PMID:Behavioural effects of NKH-477, a forskolin analogue, on locomotion and rearing in rats. 1134 75

The insect oocyte sequesters nutritive proteins during patency, which is facilitated as a result of intercellular spaces occurring between follicular epithelial cells under the influence of juvenile hormone (JH). Patency was analyzed in the moth, Heliothis virescens, using a pharmacological approach, in which we used different JH homologues and chemicals that specifically target elements of two second-messenger pathways in vertebrates, the cAMP-dependent and inositol triphosphate/diacylglycerol signaling pathways. JH I and JH III evoked dose-dependent patency in H. virescens oocyte follicles, which was suppressed by the Na/K-ATPase inhibitor, ouabain. Patency was observed in follicular epithelial cells treated with either protein kinase C activator, PDBu, or protein kinase A activator, 8-Br-cAMP, by itself. The protein kinase C inhibitor, H-7, preferentially suppressed patency evoked by JH III, whereas the protein kinase A inhibitor, H89, preferentially suppressed that evoked by JH I. Additionally, patency was triggered by the adenylate cyclase activator, NKH 477, or peptide Gs-protein activator, cholera toxin, alone. Patency evoked by JH I was suppressed by the adenylate cyclase inhibitor, SQ 22,536, and GPAnt-2, a peptide antagonistic to Gs proteins that stimulates adenylate cyclase. Neither of these latter inhibitors, however, affected JH III-evoked patency. These results suggest that, in the process of patency in H. virescens ovarial follicles, JH I predominantly signals via the cAMP-dependent second messenger system, whereas JH III acts via the inositol triphosphate/diacylglycerol signaling pathway. Moreover, stimulation of patency by cholera toxin alone and inhibition of JH I-evoked patency by GPAnt-2, strongly suggest that JH I acts on the follicular epithelial cells via activation of G-protein, and-possibly-via G(s)-protein coupled receptor.
 ...
PMID:Pharmacological analysis of ovarial patency in Heliothis virescens. 1589 Jan 88

Feeding in codling moth caterpillars was induced by the general glutamate receptor activator monosodium glutamate (MSG) and by three different mGluR agonists known to specifically stimulate different classes of vertebrate metabotropic glutamate receptors, including: (1S,3R)-ACPD, which stimulates group I mGluRs (2R,4R)-APDC, which stimulates group II mGluRs and L-AP4, which stimulates some group III mGluRs. Experiments exposing larvae to combinations of specific mGluR agonists and specific signal transduction modulators suggest that each tested mGluR uses a different signaling pathway. First, feeding stimulatory effects of (1S,3R)-ACPD were abolished by phospholipase C inhibitor, U 73122, but remained unaffected by adenylate cyclase activator, NKH 477, or phosphodiesterase inhibitor, Rolipram. Second, (2R,4R)-APDC induced feeding in presence of U 73122 or Rolipram, but lost its feeding stimulatory effects in presence of NKH 477. Finally, L-AP4 did not induce feeding in presence of Rolipram, but maintained its feeding stimulatory effects in presence of U 73122 or NKH 477. The activity of the general glutamate receptor activator MSG was abolished by NKH 477, and Rolipram. U 73122 did not affect MSG-stimulated feeding. These results suggest that transduction of MSG taste in the codling moth caterpillar relies mostly on cAMP-dependent signaling pathways.
 ...
PMID:Effect of metabotropic glutamate receptor agonists and signal transduction modulators on feeding by a caterpillar. 1636 14