Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Norbormide (NRB) is a selective vasoconstrictor agent of the rat small vessels. The mechanisms underlying the selective vasoconstrictor effect of NRB are unknown. To investigate whether phospholipase C (PLC) signaling pathway plays a role in NRB-induced vasoconstriction, we performed experiments in NRB-contracted tissues, namely, rat caudal arteries (RCA) and smooth muscle cells derived from rat mesenteric arteries (MVSMCs). An NRB-insensitive vessel, namely rat aorta (RA), served as a control tissue. In RCA and RA we measured either isometric tension or formation of inositol phosphates (IPs), the latter taken as an index of PLC activation. In MVSMCs, we measured intracellular free calcium concentration ([Ca2+]cyt). In the presence of external Ca2+, NRB (2-50 microM) stimulated IPs formation in RCA but not in RA, and increased [Ca2+]cyt in MVSMCs. In the absence of external Ca2+, NRB (50 microM) increased IPs formation in RCA but was unable to increase [Ca2+]cyt in MVSMCs. In RCA, in the presence of external Ca2+, NRB-induced contraction was inhibited by calphostin C (0.2-1 microM), an inhibitor of protein kinase C (PKC), and by SK&F 96365 (30 microM), an inhibitor of the store-operated calcium channels, but was poorly affected by verapamil, an L-type calcium channel blocker. However, verapamil was much more effective when external Ca2+ was substituted by Sr2+. These results suggest that NRB elicits its tissue and species-selective vasoconstrictor effect by stimulating PLC-PKC pathway and increasing Ca2+ influx through both verapamil-sensitive and -insensitive calcium channels. Ca2+ release from sarcoplasmic reticulum seems not involved in NRB vasoconstriction.
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PMID:Signaling mechanisms for the selective vasoconstrictor effect of norbormide on the rat small arteries. 1116 Jun 31

Norbormide is a unique vasoactive substance endowed with species- and tissue-specific, endothelium independent, vasoconstrictor activity that is restricted to the peripheral arteries of rat. In rat aorta and in all tested arteries of other species norbormide exhibits vasorelaxant property presumably due to the blockade of calcium channels. A calcium entry blocker effect of norbormide has also been described in isolated, perfused guinea pig hearts. In these preparations norbormide produced coronary vasodilator, as well as negative inotropic and dromotropic effects. In single ventricular myocytes of guinea pigs norbormide reduces L-type calcium current. The mechanism underlying the selective vasoconstrictor effect of norbormide is unknown. In rat caudal artery, a vessel contracted by norbormide, the drug activates phospholipase C (PLC) signal cascade which is the biochemical pathway involved in the contractile effect triggered by most receptor-activating vasoactive agents. Therefore, norbormide-induced contraction of rat peripheral vessels is likely to be due to the activation of a PLC-coupled receptor abundantly or selectively expressed in vascular smooth muscle cells. The identification of this putative receptor could facilitate the development of tissue-selective pharmacological agents.
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PMID:Norbormide: a calcium entry blocker with selective vasoconstrictor activity in rat peripheral arteries. 1160 40

Norbormide (N) is a vasoconstrictor agent, which acts selectively on the peripheral arteries of the rat, through the activation of the phospholipase C (PLC) cascade and the stimulation of Ca(2+) entrance in the vascular myocytes. Several endogenous vasoconstrictor agent (e.g. angiotensin-II (ANG-II) and endothelin-1 (ET-1)), that stimulate PLC pathway, are also able to enhance aldosterone secretion by the adrenal gland. Hence, we examined the effects of norbormide ((0.5, 1.0 or 5) x 10(-5)M) on corticosteroid-hormone secretion from adrenal slices of rats and mice. Quantitative HPLC assay showed that under basal conditions rat and mouse adrenal quarters secreted progesterone (PROG), 11-deoxycorticosterone (DOC), 18-hydroxy-DOC (18OH-DOC), corticosterone (CORT), 18-hydroxy-corticosterone (18OH-CORT) and aldosterone (ALDO), as well as large amounts of pregnenolone (PREG) when its metabolism was blocked by 10(-5)M cyanoketone. Norbormide concentration-dependently raised the secretion of all post-DOC steroids assayed, decreased progesterone and DOC production, and did not affect pregnenolone release. In conclusion, norbormide is able to enhance late steps of steroid synthesis, i.e. those leading to the transformation of DOC to corticosterone and aldosterone, without affecting early steps. This is an interesting finding because the other main endogenous adrenal secretagogues are known to stimulate both early and late steps of steroid synthesis. The mechanism underlying the selective activating action of norbormide on 11beta- and 18-hydroxylation remains to be investigated.
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PMID:Norbormide enhances late steps of steroid-hormone synthesis in rat and mouse adrenal cortex. 1273 93