Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004135 (ATM)
 13,001 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gly-His-Lys, a tripeptide isolated from human plasma that increases the growth rate of many cells, stimulated in dose-dependent fashion the activity of phosphorylase a in isolated rat hepatocytes. Such effect was associated to increases in both IP3 production and [Ca++]i. Interestingly, these effects of Gly-His-Lys were antagonized by losartan, a nonpeptide angiotensin II receptor antagonist (AT1 selective), which suggested that these receptors were involved in its effect. Binding competition experiments using the radioligand [125I][Sar1-Ile8]angiotensin II clearly indicated that Gly-His-Lys interacts with AT1 receptors. It was also observed that other histidine-containing tripeptides were also capable of interacting with these receptors.
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PMID:Glycyl-histidyl-lysine interacts with the angiotensin II AT1 receptor. 854 39

This study was designed to ascertain whether the extracellular loops of vasopressin/oxytocin receptors bind ligands and, if so, to locate the molecular determinants of this ligand-receptor interaction. Ligand-binding studies were employed using a rat liver V1a vasopressin receptor preparation and both peptide and non-peptide receptor ligands. Synthetic peptides corresponding to defined regions of the extracellular surface of the neurohypophysial hormone receptors recognized radioligands. These receptor mimetics inhibited the binding of radioligands to the V1a receptor with apparent affinities (pKi) ranging from 3.1 to 6.75. The same mimetics had no effects on the binding of angiotensin II to the rat AT1 receptor, indicating specificity for V1a receptor ligands. A mimetic peptide (DITYRFRGPDWL) of the first extracellular loop (ECII) of the V1a vasopressin receptor also inhibited vasopressin-stimulated, but not angiotensin II-stimulated, glycogen phosphorylase in isolated rat hepatocytes. In contrast, scrambled ECII mimetics displayed greatly reduced affinity for vasopressin. In addition, the role of peptide side-chain versus main-chain atoms in the binding of ligands by vasopressin receptors was addressed using retro-inverso peptide mimetics. Our findings indicate a precise orientation of the extracellular receptor surface (particularly the ECII domain) which facilitates the initial 'capture' of both peptide and non-peptide ligands. Moreover, the data indicate that the main-chain atoms of both a major binding-site determinant in the first extracellular loop of the receptor and the neurohypophysial hormones contribute significantly to the ligand-receptor interaction. These findings also suggest that soluble receptor-binding domains have therapeutic potential.
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PMID:Molecular recognition of peptide and non-peptide ligands by the extracellular domains of neurohypophysial hormone receptors. 871 88

Angiotensin II stimulates phosphorylase a activity and c-fos expression in isolated rat hepatocytes. Both effects are mediated through AT1 receptors. However, the time-courses and the dose-dependencies of these responses were different. These effects of angiotensin II were blocked by Losartan when the antagonist was added to the cells before the hormone or when both the hormone and the antagonist were added simultaneously. Interestingly, when the antagonist was added 2 or 3 min after the peptide hormone, the action on phosphorylase a activity was markedly decreased but, in contrast, that on c-fos expression was not affected. The data suggest that angiotensin II-mediated activation of phosphorylase a was reversible and dependent on continuous receptor activation by the hormone whereas c-fos expression did not seem to have these characteristics, i.e., our data suggest that once protooncogene expression is triggered, the process becomes independent of the hormone-receptor interaction.
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PMID:Differences between rapid and longer-term actions of angiotensin II in isolated rat hepatocytes. Effects on phosphorylase a activity and c-fos expression. 884 49

In guinea pig hepatocytes angiotensin II induced phosphorylase a activation. This effect was mimicked by other angiotensins with the potency order: angiotensin II (EC50 approximately 1 nM) > angiotensin III (EC50 approximately nM) > angiotensin I (EC50 approximately 300 nM). The effect of 10 nM angiotensin II was blocked by the angiotensin II receptor AT1-selective antagonists irbesartan and losartan (Ki values of approximately 1 nM and approximately 10 nM for irbesartan and losartan respectively) but not by the AT2-selective antagonist PD123177. Similar data were obtained when the production of [3H]IP3 from [3H]myo-inositol-labeled cells was studied Angiotensin II induced a dose-dependent increase in [3H]IP3 production; the maximal effect (approximately 3-fold) was observed at a concentration of 10 microM. This effect of angiotensin II was completely blocked by the AT1-selective antagonists irbesartan and losartan, but only in a very limited fashion by PD123177. [125I][Sar1-Ile8]angiotensin II bound with high affinity (approximately 3.8 nM) to a moderately abundant number of sites (approximately 660 fmol/mg protein) in guinea pig liver membranes. Binding competition experiments indicate the following orders of potency for agonists: angiotensin II (approximately 1.5 nM) > angiotensin III (approximately 7 nM) > angiotensin I (approximately 176 nM), and for antagonists: irbesartan (approximately 0.5 nM) > losartan (approximately 36 nM) > > PD123177 (> > 10000 nM). The functional and binding data strongly indicate that the effects of angiotensin II were mediated through AT1 receptors. Expression of the mRNA for these receptors was confirmed by RT-PCR and hybridization of the reaction product with a radiolabeled rat AT1 receptor cDNA probe.
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PMID:Characterization of the AT1 angiotensin II receptor expressed in guinea pig liver. 924 47