Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nine isoquinoline alkaloids have been isolated from the bark of Artabotrys maingayi: four noraporphines (norstephalagine, 3-hydroxynornuciferine, anonaine, and nornuciferine), one 7-hydroxyaporphine (ushinsunine), three oxoaporphines (atherospermidine, liriodenine, and lysicamine), and one protoberberine (discretamine). The effects of the main alkaloids, norstephalagine and atherospermidine, have been studied on the Ca-dependent contractile activity of smooth muscle (uterus). Both norstephalagine and atherospermidine show relaxing activity on rat uterine contractions induced by KCl or rhythmic contractions induced by oxytocin in the presence of Ca, but only atherospermidine can relax oxytocin- or vanadate-induced contractions in a Ca-free medium.
 ...
PMID:[Norstephalagine and atherospermidine: two smooth muscle relaxant aporphines from Artabotrys maingayi]. 238 Jul 22

The effects of natriuretic peptides on electrical activity and cellular cGMP levels were studied in neurons of the supraoptic nucleus (SON) of rat hypothalamic slice preparations. Intracellular and extracellular recordings showed that bath application of A type natriuretic peptide (ANP) at 100 nM or B type natriuretic peptide (BNP) at 100 to 300 nM decreased the firing rate and hyperpolarized the membrane potential in phasically firing (putative vasopressin) neurons. Non-phasically firing (putative oxytocin) neurons did not respond to these natriuretic peptides in firing rate or membrane potential. The membrane-permeable cGMP analogue 8-bromo cGMP at 0.5 mM and the phosphodiesterase inhibitor 3/isobutyl-1-methylxanthine (IBMX) at 50 microM mimicked the inhibitory effects of ANP and BNP. The specific inhibitor of cGMP phosphodiesterase 1-(3-chloroanilino)-4-phenylphthalazine+ ++ (MY5445) at 30 microM also decreased the firing rate of SON neurons. The cGMP-dependent protein kinase inhibitor N-(2-(methylamino)ethyl)-5-isoquinoline-sulfonamide dihydrochloride (H8) at 1 microM abolished the inhibition by natriuretic peptides. We measured cGMP and cAMP contents in discrete SON regions and compared the change of contents before and after application of ANP and BNP. The increases in cellular cGMP accumulation were 430% for ANP and 120% for BNP, although they did not cause significant change of cAMP accumulation. The results suggest that the inhibitory effects of natriuretic peptides on putative vasopressin neurons are mediated through cGMP and cGMP-dependent protein kinase.
 ...
PMID:Inhibitory effects of natriuretic peptides on vasopressin neurons mediated through cGMP and cGMP-dependent protein kinase in vitro. 868 Apr 19

Protein kinases have an important role in signal transduction in the cellular system via protein phosphorylation. RhoA activated Rho-kinases have a pivotal role in the regulation of smooth muscle contraction. ROCK I and ROCK II phosphorylate myosin-phosphatase and myosin-kinase, which induces contraction in the myometrium. Several studies have investigated the affinity of isoquinoline alkaloids (HA-1077, H1152P) to Rho-kinases, and these compounds notably inhibited the Ca2+-independent process. We measured the efficiency of 25 original, newly synthesized isoquinoline derivatives for the Rho-kinase activity using Rho-associated kinase activity assay and determined their effects on the non-pregnant, 20-day pregnant and parturient rat myometrial contraction in vitro. The IC50 values of 11 from among the 25 derivatives were significantly lower on the oxytocin-induced non-pregnant rat uterine contraction compared with Y-27632 and fasudil, although their maximal inhibitory effects were weaker than those of Y-27632 and fasudil. We measured the effects of 11 isoquinoline molecules with significant IC50 values on ROCK II activity. We found two isoquinolines out of 11 compounds (218 and 852) which decreased the active ROCK II level similarly as Y-27632. Then we found that 218 and 852 relaxed the 20th-day pregnant and parturient rat uterus with greater potency as compared with fasudil. The majority of the synthesized isoquinoline derivatives have uterus relaxant effects and two of them significantly suppress the Rho-kinase mediated myosin light chain phosphorylation. Our results may suggest that the isoquinoline structure has a promising prospect for the development of new and effective inhibitors of uterine contractions in preterm birth.
 ...
PMID:Effects of newly synthetized isoquinoline derivatives on rat uterine contractility and ROCK II activity. 2926 16