Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2-Mercapto-1-(beta-4-pyridethyl) benzimidazole (MPB) was originally introduced as a reversible inhibitor of RNA synthesis, but subsequent findings made this suggestion doubtful. We examined the effect of MPB on active sodium transport, measured as short-circuit current (scc), across the isolated urinary bladder of the toad (Bufo marinus). The drug caused a rapid, dose-dependent inhibition of baseline scc; 25 micrograms/ml MPB reduced it by 70%. Sensitivity to MPB was the same in the presence and absence of metabolizable substrate. The transport stimulation by aldosterone (7 X 10(-8)M) was abolished entirely when MPB was introduced 30 min before the hormone. In bladders incubated with MPB with or without aldosterone, removal of both agents resulted in a rise in scc, which was more rapid in the aldosterone-pretreated hemibladders; a significant difference was observed after 30 min. This suggests that MPB inhibited transport at a site distal to messenger RNA accumulation. The effect of 3 hr of pretreatment with MPB on the response of the bladders to antidiuretic hormone (ADH, 20 mU) and cyclic AMP (cAMP, 10 mM) was then examined. The absolute increment in scc due to these agents was the same as in the absence of MPB, though the baseline was much reduced by the drug. After challenging MPB-pretreated bladders with theophylline (22.5 mM), sodium transport rose continuously for 90 min, in contrast to the small, short-lived rise in the absence of MPB. It is proposed that, in the toad bladder, MPB may: (1) inhibit cAMP-dependent protein kinase, as found by us in other tissues; and (2) counteract the accumulation of a transport inhibitor, possibly calcium or cyclic GMP, in tissues treated with endogenous or exogenous cAMP.
 ...
PMID:2-Mercapto-1-(beta-4-pyridethyl) benzimidazole inhibition of basal and aldosterone-stimulated sodium transport but prolongation of the transient theophylline-induced stimulation in the toad bladder. 619 73

It is often believed that increases in intracellular Ca2+ ([Ca2+]i) resulting from stimulation of G-protein coupled receptors in vascular smooth muscle cells (VSMC) require activation of the beta1 isoform of phospholipase C (PLC). However, recent studies showed that rat aortic VSMC do not express PLC beta-1 and that stimulation with angiotensin-II induces tyrosine kinase dependent increases in [Ca2+]i and tyrosine phosphorylation of PLC gamma-1. Whether this pathway is activated by other vasoactive agents that stimulate G-protein coupled receptors is unknown. Here, we show that A10 VSMC express PLC beta-2, PLC beta-3, PLC delta-1, and PLC gamma-1. The cells also expressed Galpha(q/11). However, neither PLC beta-1 nor PLC beta-4 was detected. Stimulation with angiotensin-II, vasopressin, serotonin, or endothelin induced tyrosine kinase dependent increases in [Ca2+]i. However, tyrosine phosphorylation of PLC gamma-1 did not occur. In contrast, stimulation with platelet derived growth factor increased [Ca2+]i and tyrosine phosphorylation of PLC gamma-1. The results show that tyrosine phosphorylation of PLC gamma-1 is not required for tyrosine kinase dependent increases in [Ca2+]i resulting from stimulation of diverse G-protein coupled receptors in VSMC.
 ...
PMID:Stimulation of G-protein coupled receptors in vascular smooth muscle cells induces tyrosine kinase dependent increases in calcium without tyrosine phosphorylation of phospholipase C gamma-1. 947 75