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

We characterized a new iodinated, high affinity, linear V1a vasopressin antagonist, phenylacetylD-Tyr(Et)Phe-Gln-Asn-Lys-Pro-Arg-Tyr-NH2. The antagonist bound specifically to the V1a vasopressin receptor in crude rat liver membranes with an apparent Kd value of 0.168 nM. This affinity is approximately 1 order of magnitude greater than that of the natural agonist, vasopressin. The inhibitory activity of the antagonist can be demonstrated by its inability to elicit activation and uncoupling of G proteins from the receptor. Thus, after occupancy of receptor sites in rat liver membranes with labeled antagonist and detergent solubilization, the labeled receptor (approximately 60 kDa) was eluted as a stable 400-kDa complex on size-exclusion chromatography. In contrast, when the receptor sites were occupied by the agonist [3H]vasopressin, the receptor eluted as a 60-kDa peak. Coincubation of membranes with iodinated antagonist and an excess of unlabeled vasopressin caused both reduced antagonist binding and a complete shift from the 400-kDa to the 60-kDa peak. The addition of vasopressin to unliganded 400-kDa fractions resulted in a 75% increase in [35S]guanosine-5'-O-(3-thio)triphosphate binding activity, indicating that the 400-kDa fraction contains complexes between the V1a receptor and G proteins. The vasopressin-elicited increase was inhibited by antagonist. Using specific antibodies and immunoadsorption to protein A/Sepharose columns, we found that G protein isotypes G(alpha q/11), G(alpha i3), and G(alpha s), and effector enzymes PLC-beta1, PLC-gamma2 and PLA-2 were associated with the antagonist-labeled receptor in the 400-kDa fraction. Because the 400-kDa complex was found in the absence of ligand, the V1a receptor and the appropriate G proteins and effector enzymes are likely preassociated with each other and do not aggregate after antagonist addition. The association of V1a receptor with the different specific G proteins and effector enzymes is consistent with the multiple actions of vasopressin on liver cells. Antibodies directed against a portion of the carboxyl-terminal domain of the V1a receptor interacted with 60-kDa antagonist-occupied receptor but not with receptor in the 400-kDa complex. These results suggest that the carboxyl-terminal region of the receptor is sterically hindered when coupled to G proteins. The iodinated linear vasopressin antagonist therefore allows stable receptor/G protein complexes and can be an important tool (along with the antisera) for use in the study of factors that control V1a receptor/G protein coupling.
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PMID:A new linear V1A vasopressin antagonist and its use in characterizing receptor/G protein interactions. 920 26

ACLMT is a myotoxic Lys49 phospholipase A(2) isolated from the venom of the snake Agkistrodon contortrix laticinctus. We have previously shown that ACLMT increases baseline water transport and partially inhibits vasopressin-stimulated water transport across toad bladders due to an increase in cytosolic calcium. However, these evidences provide insufficient insight into the mechanisms involved in the effects of ACLMT on membrane permeability. In an attempt to better understand such mechanisms, the current study aimed to investigate whether the Na(+)/K(+)-ATPase activity of isolated toad bladders can be affected by the ACLMT and the synthetic peptide from its C-terminal region. The toxin significantly decreased the Na(+)/K(+)-ATPase, while the peptide did not alter it. These findings suggest that the effects of ACLMT on membrane permeability may be due to the inhibition of the Na(+)/K(+)-ATPase activity, and that the C-terminal region may not play a relevant role in this effect. This study contributes toward a better understanding of the mechanisms involved in the toxicity of the snake venom Lys49 PLA(2) myotoxins on biological tissues.
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PMID:The effect of the myotoxic Lys49 phospholipase A(2) from Agkistrodon contortrix laticinctus snake venom on Na+/K+ -ATPase activity of toad bladders. 1679 14

We have previously shown that centrally injected melittin, a phospholipase A(2) (PLA(2)) activator, increases blood pressure and decreases heart rate in the normotensive conscious rats. In the current study we aimed to determine the cardiovascular effects of melittin in hemorrhaged hypotensive rats and to investigate the mediation of peripheral adrenergic, vasopressinergic and renin angiotensin system in the pressor effect of centrally administrated melittin in both normotensive and hypotensive conditions. Acute hypotensive hemorrhage was performed by withdrawing a total volume of 2.2ml of blood/100g body weight over a period of 10min. Melittin was injected intracerebroventricularly (i.c.v.) at the doses of 1.5microg, 3.0microg or 6.0microg after the stabilization period of hemorrhage procedure. We also repeated previous experiments by injecting melittin (1.5microg, 3.0microg or 6.0microg; i.c.v.) to the normotensive animals. Melittin caused dose- and time-dependent increases in mean arterial pressure (MAP) in normal and hypotensive conditions and decreases in heart rate (HR) in normotensive conscious animals. In hypotensive rats, melittin injected at the dose of 6.0microg completely restored the decrease in blood pressure. Plasma adrenaline, noradrenaline, vasopressin levels and renin activity increased after melittin (3.0microg; i.c.v) administration in normal conditions. Hemorrhage, itself, produced an increase in these plasma hormone levels and melittin (3.0microg; i.c.v.) caused additional increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity in hypotensive conditions. Intravenous pretreatments of rats with prazosin (0.5mg/kg), an alpha(1) adrenoceptor antagonist, [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Me-Tyr(2)-Arg(8)]-vasopressin (10microg/kg), a vasopressin V(1) receptor antagonist, or saralasin (250microg/kg), an angiotensin II receptor antagonist, partially blocked the pressor response to melittin (3.0microg; i.c.v.) in both normotensive and hypotensive conditions. Besides, the combined administration of these three antagonists before melittin completely abolished the pressor responses to drug in both conditions. Results show that centrally administered melittin, a PLA(2) activator, increases blood pressure and reverses hypotension in hemorrhagic shock. The increases in plasma adrenaline, noradrenaline, vasopressin levels and renin activity mediate the pressor responses to melittin in normal and hypotensive conditions.
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PMID:Cardiovascular effects of centrally injected melittin in hemorrhaged hypotensive rats: the investigation of peripheral mechanisms. 1789 13