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)

Intracellular pH (pHi), apical membrane potential (Va), and fractional apical membrane resistance (FRa) were measured in principal cells of isolated frog skin (Rana pipiens) with double-barreled microelectrodes under short-circuit conditions. Basolateral exposure to 10 mU/ml arginine vasotocin (AVT) depolarized Va by 30 mV, decreased FRa by 33%, increased short-circuit current (Isc) by 17 microA, and increased pHi by 0.17 pH units. The response of Va, Isc, and pHi occurred concurrently. Forskolin, theophylline, and 8-(4-chlorophenyl-thio)-adenosine 3',5'-cyclic monophosphate caused similar changes in Va, Isc, and pHi. The enhanced response of Isc, Va, and FRa to short pulses of apical amiloride applied during AVT or cAMP exposure suggests an increase in apical Na+ conductance. The presence of cAMP agonists also enhanced the response of pHi to amiloride. We conclude that the AVT- and cAMP-induced increase in Na+ transport across the apical cell membrane is associated with a change in pHi. These data are consistent with the hypothesis that changes in pHi may play a role in the second messenger cascade initiated by the antidiuretic hormone.
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PMID:Na+ transport and pH in principal cells of frog skin: effect of antidiuretic hormone. 804 13

Cytosolic free calcium concentration ([Ca2+]i) was measured in single microdissected rat medullary collecting tubules [outer (OMCD) and inner (IMCD)] to identify receptors involved in vasopressin (AVP)-induced [Ca2+]i increases. In both segments, [Phe2,Orn8]vasotocin ([Phe2,Orn8]VT), a specific V1 agonist, as well as the V2 agonist 1-desamino-8-D-AVP (dDAVP) triggered [Ca2+]i variations. In OMCD, the mean response to 10 nM AVP roughly corresponded to the sum of V1 and V2 agonists effects. In IMCD, dDAVP (10 nM) alone reproduced the calcium response to AVP (delta[Ca2+]i = 243 +/- 34 nM, n = 6, and 248 +/- 27 nM, n = 8, with dDAVP and AVP, respectively). Furthermore, in the same experiments V1 and V2 maximal effects were not additive ([Phe2,Orn8]VT = 154 +/- 21 nM, n = 6; dDAVP + [Phe2,Orn8]VT = 233 +/- 23 nM, n = 9). As AVP, dDAVP released intracellular calcium (delta[Ca2+]i in calcium-free medium = 182 +/- 24 nM, n = 8, vs. 182 +/- 14 nM, n = 6 with 10 nM dDAVP and AVP, respectively). Neither 8-(4-chlorophenyl-thio)-adenosine 3',5'-cyclic monophosphate nor forskolin modified [Ca2+]i. A cross-reaction of dDAVP with an oxytocin (OT) receptor can be excluded since 1) the specific OT agonist [Thr4,Gly7]OT (10 nM) increased only slightly [Ca2+]i (delta-[Ca2+]i = 20 +/- 5 nM, n = 11); 2) the dDAVP response was not altered by the specific OT antagonist [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid),2-(O-methyl)tyrosine,4-threonine, 8-ornithine,9-tyrosylamide]vasotocin [d(CH2)5(1),O-Me-Tyr2,Thr4,Tyr-NH2(9)]OVT; 3) it was insensitive to V1 antagonists but was totally blocked by the V1/V2 antagonist [d(CH2)5(1),O-Et-Tyr2,Val4]AVP ([delta[Ca2+]i = 18 +/- 4 nM, n = 6). These results indicate that in IMCD AVP increases [Ca2+]i via both V1 and V2 receptors. [Ca2+]i variations due to V2 receptors involve a mechanism independent of adenylate cyclase and coupled to the same intracellular calcium pool as V1 and V2 receptors.
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PMID:V2-like vasopressin receptor mobilizes intracellular Ca2+ in rat medullary collecting tubules. 834 13

The effects of urea structural analogues on the urea-facilitated diffusion system were examined in human red cell membranes (pink ghosts) and in antidiuretic hormone(ADH)-stimulated frog urinary bladder epithelia. In both tissues, urea permeability (P(urea)) was dramatically but reversibly inhibited by a number of urea analogues, such as 1-(3,4-dichlorophenyl)-2-thiourea (DCPTU). This urea derivative reduced the urea flux in a dose-dependent manner (90% inhibition of P(urea) at 0.5 mM concentration of DCPTU). With the aim of obtaining irreversible markers of red cell and urinary bladder urea transport systems, urea derivatives were modified by addition of an azido residue (N3) and preliminary experiments of photoaffinity labelling were carried out. Two synthetic urea derivatives: 1-(3-azido-4-chlorophenyl)-2-thiourea (ACPTU) and 1-(3-azido-4-chlorophenyl)-3-methyl-2-thiourea (Me-ACPTU) were shown to be very potent inhibitors of P(urea) when used in the absence of light, with IC50 values 60.3 microM and 31.6 microM respectively, as measured in frog urinary bladder. Both these molecules appeared to bind covalently to the urea carrier in both frog urinary bladder and human pink red cell ghosts, when illuminated in the presence of the tissue: the urea flux, which fell to 30-70% of the value obtained in the presence of ADH after inhibitor addition, remained low after the preparation had been illuminated for 30 min and the inhibitor removed. These results provide an interesting approach to the urea carrier analysis, particularly to the urea or urea analogue binding site on the transport protein.
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PMID:Urea derivatives as tools for studying the urea-facilitated transport system. 848 92

Activation of peripheral cannabinoid CB(1) receptors elicits hypotension. Using the radioactive microsphere technique, we examined the effects of cannabinoids on systemic hemodynamics in anesthetized rats. The potent cannabinoid CB(1) receptor agonist HU-210 ([-]-11-OH-Delta(9) tetrahydrocannabinol dimethylheptyl, 10 microg/kg i.v.) reduced mean blood pressure by 57+/-5 mm Hg by decreasing cardiac index from 37+/-1 to 23+/-2 ml/min/100 g (P<0.05) without significantly affecting systemic vascular resistance index. HU-210 elicited a similar decrease in blood pressure following ganglionic blockade and vasopressin infusion. The endogenous cannabinoid anandamide (arachidonyl ethanolamide, 4 mg/kg i.v.) decreased blood pressure by 40+/-7 mm Hg by reducing systemic vascular resistance index from 3.3+/-0.1 to 2.3+/-0.1 mm Hg min/ml/100 g (P<0.05), leaving cardiac index and stroke volume index unchanged. HU-210, anandamide, and its metabolically stable analog, R-methanandamide, lowered vascular resistance primarily in the coronaries and the brain. These vasodilator effects remained unchanged when autoregulation was prevented by maintaining blood pressure through volume replacement, but were prevented by pretreatment with the cannabinoid CB(1) receptor antagonist SR141716A (N-[piperidin-1-yl]-5-[4-chlorophenyl]-1-[2,4-dichlorophenyl]-4-methyl-1H-pyrazole-3-carboxamide HCl; 3 mg/kg i.v.). Only anandamide and R-methanandamide were vasodilators in the mesentery. We conclude that cannabinoids elicit profound coronary and cerebral vasodilation in vivo by direct activation of vascular cannabinoid CB(1) receptors, rather than via autoregulation, a decrease in sympathetic tone or, in the case of anandamide, the action of a non-cannabinoid metabolite. Differences between the hemodynamic profile of various cannabinoids may reflect quantitative differences in cannabinoid CB(1) receptor expression in different tissues and/or the involvement of as-yet-unidentified receptors.
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PMID:Hemodynamic effects of cannabinoids: coronary and cerebral vasodilation mediated by cannabinoid CB(1) receptors. 1144 86

The ubiquitously expressed canonical transient receptor potential (TRPC) ion channels are considered important in Ca2+ signal generation, but their mechanisms of activation and roles remain elusive. Whereas most studies have examined overexpressed TRPC channels, we used molecular, biochemical, and electrophysiological approaches to assess the expression and function of endogenous TRPC channels in A7r5 smooth muscle cells. Real time PCR and Western analyses reveal TRPC6 as the only member of the diacylglycerol-responsive TRPC3/6/7 subfamily of channels expressed at significant levels in A7r5 cells. TRPC1, TRPC4, and TRPC5 were also abundant. An outwardly rectifying, nonselective cation current was activated by phospholipase C-coupled vasopressin receptor activation or by the diacylglycerol analogue, oleoyl-2-acetyl-sn-glycerol (OAG). Introduction of TRPC6 small interfering RNA sequences into A7r5 cells by electroporation led to 90% reduction of TRPC6 transcript and 80% reduction of TRPC6 protein without any detectable compensatory changes in the expression of other TRPC channels. The OAG-activated nonselective cation current was similarly reduced by TRPC6 RNA interference. Intracellular Ca2+ measurements using fura-2 revealed that thapsigargin-induced store-operated Ca2+ entry was unaffected by TRPC6 knockdown, whereas vasopressin-induced Ca2+ entry was suppressed by more than 50%. In contrast, OAG-induced Ca2+ transients were unaffected by TRPC6 knockdown. Nevertheless, OAG-induced Ca2+ entry bore the hallmarks of TRPC6 function; it was inhibited by protein kinase C and blocked by the Src-kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine (PP2). Importantly, OAG-induced Ca2+ entry was blocked by the potent L-type Ca2+ channel inhibitor, *nimodipine. Thus, TRPC6 activation probably results primarily in Na ion entry and depolarization, leading to activation of L-type channels as the mediators of Ca2+ entry. Calculations reveal that even 90% reduction of TRPC6 channels would allow depolarization sufficient to activate L-type channels. This tight coupling between TRPC6 and L-type channels is probably important in mediating smooth muscle cell membrane potential and muscle contraction.
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PMID:Role of endogenous TRPC6 channels in Ca2+ signal generation in A7r5 smooth muscle cells. 1620 51

The discovery of a novel series of 8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl) propanamide antagonists of the vasopressin V(1A) receptor is disclosed. Compounds 47 and 48 were found to be high affinity, selective vasopressin V(1A) antagonists.
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PMID:The discovery of novel 8-azabicyclo[3.2.1]octan-3-yl)-3-(4-chlorophenyl) propanamides as vasopressin V1A receptor antagonists. 2145 61