Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Desensitization of vasopressin V2 receptor-mediated adenylate cyclase was studied in canine kidney cell line, MDCK cells. Overnight treatment of MDCK cells with arginine vasopressin (AVP) resulted in a loss of vasopressin receptors and an inhibition of cAMP accumulation in response to AVP. Both the loss of receptor and reduction in cAMP accumulation were time- and AVP concentration-dependent. Desensitization was selective for AVP because cAMP formation in response to isoproterenol, prostaglandin E1 (PGE1) and forskolin was not affected by AVP pre-treatment. Pre-treatment of MDCK cells with phorbol dibutyrate (PDBu) also caused a dose-dependent inhibition of AVP mediated cAMP accumulation, but not of isoproterenol-, PGE1- and forskolin-induced cAMP accumulation. PDBu pre-treatment did not cause loss of vasopressin receptors. Instead, the affinity for vasopressin was changed by PDBu treatment. Pre-treatment of the cells with pertussis toxin (PT) had no effect on the desensitization and downregulation of vasopressin (V2) receptors, suggesting that the desensitization may not be mediated by pertussis toxin sensitive G-protein. Our data suggest that pre-treatment of MDCK cells with AVP or PDBu caused desensitization of AVP-mediated cAMP accumulation and that downregulation of V2 receptors required agonist occupancy of the receptors, whereas the affinity of the receptors was changed by phorbol ester treatment.
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PMID:Desensitization of vasopressin sensitive adenylate cyclase by vasopressin and phorbol esters. 216 86

Administration of adenosine (Ado) into rat renal artery induces dose-dependent diuresis that is independent of changes in glomerular filtration rate or renal blood flow, suggesting a direct effect on tubule H2O reabsorption. To test the hypothesis that Ado modulates cellular action of arginine vasopressin (AVP) as a tubular mechanism for the diuretic effect of Ado, interaction of Ado with AVP was studied in primary cell culture of rat inner medullary collecting duct (IMCD) epithelium. Stimulation of cells with 10(-6) M AVP in presence of 0.1 mM Ro 20-1724, a nonmethylxanthine phosphodiesterase inhibitor that has no effect on Ado receptors, increased adenosine 3',5'-cyclic monophosphate (cAMP) levels twofold or more above baseline. Stimulation of cells with the A1 Ado-receptor agonist N6-cyclohexyladenosine (CHA), the A2-receptor agonist 5'-(N-ethylcarboxamido)-adenosine (NECA), or with the P-site agonist 2',5'-dideoxyadenosine (DDA) significantly inhibited the AVP-stimulated cAMP response. Preincubation with pertussis toxin abolished the inhibitory effects of CHA and NECA, but not of DDA. The data suggest that, in the rat IMCD, Ado modulates AVP action by interfering with its ability to stimulate formation of its second messenger, cAMP. This effect is mediated by the extracellular Ado receptors A1 and A2 and by the intracellular P-site. It occurs by at least two pathways, one sensitive and the other insensitive to pertussis toxin.
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PMID:Interaction of adenosine with vasopressin in the inner medullary collecting duct. 217 61

By employing early-passaged rabbit kidney epithelial cells in tissue culture, we demonstrated that angiotensin II (AII) has unique mechanisms of signal transduction. First, unlike its action in other target tissues, micromolar concentrations of AII are required to induce small rises in cytosolic calcium, [Ca2+]i, an action which is not accompanied by the release of inositol phosphates (IP). In contrast, nanomolar bradykinin (BK) mobilizes [Ca2+]i through activation of phospholipase C and release of IP. Neither of these stimulated calcium responses exhibits pertussis toxin (PTx) sensitivity. Secondly, AII and BK at 10(-9) to 10(-7) M stimulate cAMP indirectly through PGE2 production in distal cells. AII- and BK-stimulated PGE2 release is PTx inhibitible, suggestive of the presence of a GTP binding protein mediating the response. By contrast, arginine vasopressin fails to elicit rises in [Ca2+]i but exerts its primary effect on cAMP production in distal cells via direct coupling to a stimulatory GTP binding protein, as evidenced by uncoupling with cholera toxin. Regulation of PGE2 synthesis appears to occur via phospholipase A2, not C, by all three peptides.
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PMID:Relationship between phospholipase C activation and prostaglandin E2 and cyclic adenosine monophosphate production in rabbit tubular epithelial cells. Effects of angiotensin, bradykinin, and arginine vasopressin. 244 59

Vasopressin (V2) receptors were solubilized from porcine kidney membranes with the detergent egg lysolecithin. Binding of [3H]vasopressin to the solubilized fraction was rapid, specific, and saturable. The agonist dissociation constants observed in membranes and solubilized fractions were 1.7 +/- 0.3 and 2.3 +/- 0.2 nM, respectively. In competition binding experiments, the solubilized fraction exhibited the same pharmacological profile as the membranes. Chemical crosslinking of [125I]vasopressin to the solubilized fraction followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated a 62-kDa band which was specifically labeled with [125I]vasopressin. Vasopressin binding sites from the solubilized fractions were resolved by gel filtration and ultracentrifugation on a sucrose gradient. In addition, agonist high affinity binding to V2 receptors and its sensitivity to guanine nucleotides were preserved even after solubilization in the absence of prebound agonist prior to solubilization. Addition of guanine nucleotides such as GTP gamma S decreased the specific binding of [3H]arginine vasopressin to these solubilized fractions in a dose-dependent manner, suggesting the solubilization of a V2 receptor-G protein complex. [32P]ADP ribosylation of the solubilized fraction by cholera and pertussis toxins revealed specifically labeled proteins with molecular weights of 42,000-43,000 and 39,000-41,000, respectively, on sodium dodecyl sulfate polyacrylamide gels. Furthermore [35S]GTP gamma S binding to these solubilized fractions was enhanced by vasopressin, confirming that a significant proportion of the vasopressin receptors must be closely coupled to G proteins even when these receptors are solubilized in the absence of agonist. These results are in contrast with those reported for beta, alpha 2 adrenergic and D2 dopaminergic receptor systems, but in agreement with D1 dopaminergic and A1 adenosine receptors. The molecular mechanism responsible for this difference remains to be determined.
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PMID:Solubilization of a guanine nucleotide-sensitive form of vasopressin V2 receptors from porcine kidney. 252 56

It is well established that in the pituitary gland corticotropin-releasing hormone (CRH) stimulates the release of beta-endorphin (beta-E) via a cAMP-linked mechanism. Studies of the mechanisms underlying the CRH stimulation of beta-E release from rat hypothalamic slices perifused in vitro are reported in this paper. The data indicate that both a cAMP-dependent and non-cAMP-dependent mechanism mediate the action of CRH in the hypothalamus. The presence of a cAMP-linked mechanism was suggested by the finding that cholera toxin (0.1-10 nM) and forskolin (2.5 x 10(-6) M), both of which act to raise intracellular cAMP levels, stimulated the release of beta-E. In both cases, no further stimulation was seen upon addition of CRH (10(-8)M). However, it was also found that preincubation of the tissue with pertussis toxin (PTX; 100 ng/ml) prevented both the CRH- and forskolin-stimulated release of beta-E. This indicated that, in addition to the cAMP-linked mechanism, a further messenger system which is connected to a PTX-sensitive G-protein may also play a role. The latter observation also implied that a further substance, which utilizes a separate second messenger system, might be involved in the CRH stimulation of beta-E release. In this regard the role of arginine vasopressin (AVP) was investigated due to the known interaction between CRH and AVP in the pituitary gland. AVP (10(-12) to 10(-6)M) itself potently and dose-dependently stimulated beta-E release, producing a maximal increase of 220% above basal levels. The AVP-induced release of beta-E was abolished in PTX-pretreated hypothalami. The apparently obligatory requirement of AVP for the CRH-stimulation of beta-E release was illustrated by the finding that blockade of AVP receptors using the AVP antagonist d(CH2)5 [Tyr(OEt)2,Val4]-AVP almost completely attenuated the CRH-stimulated release of beta-E. Furthermore, in the presence of a high concentration of AVP (10(-6)M) no further stimulation of release was seen with CRH (10(-8)M). These data therefore strongly indicate that CRH acts via the intermediacy of AVP to release beta-E from hypothalamic slices in vitro and that two separate second messenger systems are involved: a cAMP-linked mechanism connected to a cholera toxin-sensitive G-protein (CRH) and a second system linked to a PTX-sensitive G-protein (AVP).
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PMID:A two-step mechanism by which corticotropin-releasing hormone releases hypothalamic beta-endorphin: the role of vasopressin and G-proteins. 252 50

The effects of arginine vasopressin (AVP) on the cytosolic free calcium concentration ([Ca2+]f) were examined in freshly immunodissected rabbit cortical collecting tubule cells using fluorescent Ca2+ indicators fura-2 and indo-1. The addition of AVP to a cell suspension resulted in a rapid and transient increase in the [Ca2+]f. The 1-deamino-8-D-AVP (dDVP), a V2 receptor agonist of AVP that stimulated adenosine 3',5' cAMP production in these cells, had no effect on [Ca2+]f and did not affect AVP-induced increase in [Ca2+]f. The AVP-induced increase in [Ca2+]f but not cAMP production was blocked by the V1 receptor antagonist, [1-(beta-mercapto-beta-beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine] Arg8-vasopressin. The AVP-stimulated increase in [Ca2+]f appeared to be largely due to Ca2+ release from intracellular stores as reduction of extracellular Ca2+ with EGTA had little if any effect on the AVP-induced increase in [Ca2+]f. This AVP-induced increase in [Ca2+]f was associated with an increase in inositol-1,4,5-trisphosphate production and appeared to involve a guanine nucleotide-binding protein (G), since the pretreatment of cells with pertussis toxin for 4-6 h inhibited this effect. Finally, measurements of [Ca2+]f in single cells suggest that only the principal cells of the collecting tubules respond to AVP with an increase in [Ca2+]f. In summary, these results demonstrate that the principal cells of the cortical collecting tubule possess two distinct receptor systems for vasopressin, the well-known V2 receptor coupled to adenylate cyclase, and a V1 receptor system that leads to the mobilization of cytosolic calcium, coupled through a pertussis toxin substrate (G protein) to a production of inositol phosphates.
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PMID:Vasopressin V1 receptors on the principal cells of the rabbit cortical collecting tubule. Stimulation of cytosolic free calcium and inositol phosphate production via coupling to a pertussis toxin substrate. 253 47

We have examined the regulation by prostaglandin E2 (PGE2) of hormone-induced adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in cells isolated by immunodissection from both the medullary and cortical thick ascending limb of Henle's loop of rabbit kidney. At concentrations greater than 10(-8) M, PGE2, but not sulprostone (16-phenoxy-17,18,19,20-tetranor-PGE2 methylsulfonilamide), caused cAMP accumulation in both cortical and medullary thick limb cells. However, at concentrations of less than or equal to 10(-8) M, both PGE2 and sulprostone inhibited arginine vasopressin (AVP)-, calcitonin-, and glucagon-induced cAMP accumulation in medullary thick ascending limb (mTAL) cells. In cortical thick limb (cTAL) cells, sulprostone also inhibited AVP-, calcitonin-, and parathyroid hormone (PTH)-induced cAMP accumulation. The inhibitory effects of PGE2 and of sulprostone were blocked by pretreatment of mTAL and cTAL cells with pertussis toxin. Membranes prepared from mTAL cells exhibited a [3H]PGE2 binding activity that was stimulated on addition of the stable guanosine 5'-triphosphate (GTP) analogue, 5'-guanosine gamma-thiotriphosphate (GTP gamma S); moreover, sulprostone inhibited [3H]PGE2 binding. Our results suggest that PGE2 can function via a prostaglandin E receptor linked to a guanine nucleotide regulatory protein, Gi, to attenuate hormone-induced cAMP formation in both mTAL and cTAL cells of rabbit kidney.
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PMID:Regulation of cAMP metabolism by PGE2 in cortical and medullary thick ascending limb of Henle's loop. 253 67

Neuropeptide Y (NPY) is a unique 36-amino acid peptide found in high concentrations in brain and peripheral neurons. Although NPY is present in kidney tissue, its role in regulation of renal function has not been delineated. We found that NPY significantly decreases arginine vasopressin (AVP) but not adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated hydraulic conductivity (Lp) in perfused rat cortical collecting tubules (CCT). Either alpha 2-adrenergic receptor blockade (yohimbine) or occupancy (clonidine) prevent NPY inhibition of AVP-stimulated Lp. By contrast, alpha 1-adrenergic receptor blockade with prazosin did not alter NPY inhibition of AVP action. Pretreatment of CCT with pertussis toxin also abolishes NPY inhibition of AVP-stimulated Lp. These data suggest that NPY acts via an alpha 2-adrenergic receptor coupled to a pertussis toxin-sensitive protein to inhibit AVP-stimulated cAMP formation and Lp in the rat CCT.
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PMID:Mechanism of neuropeptide Y inhibition of vasopressin action in rat cortical collecting tubule. 253 78

The mechanism of Ca2+ influx stimulated by arginine vasopressin (AVP) was studied in cultured rat smooth muscle cells. AVP stimulated 45Ca2+ influx even in the presence of nifedipine, a Ca2+ antagonist that inhibits voltage-dependent Ca2+ channel. NaF, a GTP-binding protein activator, mimicked the AVP-stimulated 45Ca2+ influx. The 45Ca2+ influx stimulated by a combination of AVP and NaF was not additive. The affinity of AVP receptor was decreased by guanosine 5'-O-(3-thiotriphosphate). Pertussis toxin failed to affect the AVP-stimulated 45Ca2+ influx. AVP did not stimulate cAMP production, but increased inositol trisphosphate generation. Both AVP-stimulated 45Ca2+ influx and inositol trisphosphate generation were inhibited by neomycin, a phospholipase C inhibitor, in a dose-dependent manner, and the patterns of both inhibitions were similar. These results suggest that, in rat smooth muscle cells, AVP-stimulated Ca2+ influx is mediated exclusively through phosphoinositide hydrolysis.
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PMID:Ca2+ influx stimulated by vasopressin is mediated by phosphoinositide hydrolysis in rat smooth muscle cells. 254 69

The adrenergic nervous system profoundly alters water excretion by both renal and extrarenal pathways. The effects of catecholamines on cultured rat inner medullary collecting tubule cells were studied. The beta-adrenergic agonist, isoproterenol, increases cAMP from 19.5 +/- 2.3 to 79.4 +/- 14.4 fm/micrograms protein, P less than 0.001. The response to arginine vasopressin (AVP) is also greater in the presence of isoproterenol, but the increment is unchanged when compared to that seen in the absence of AVP. The agonist effect of isoproterenol is blocked by propranolol but not by the specific beta 1 antagonist, atenolol. The effect of alpha-adrenergic stimulation was studied by the use of norepinephrine (NE) in the background of the beta blocker, propranolol. NE decreases AVP-stimulated cAMP generation from 190 +/- 11 to 117 +/- 10 fm/micrograms, P less than 0.001, N = 6. The specific alpha 2 antagonist, yohimbine, but not the alpha 1 antagonist, prazosin, prevents the NE-induced decrease as AVP-stimulated cAMP is restored to 187 +/- 19 fm/micrograms. Similarly the selective alpha 2 agonist, clonidine, significantly inhibits both AVP- and isoproterenol-mediated cAMP generation. To define the site of alpha 2 inhibition in the adenylate cyclase (AC) complex the effect of pertussis toxin (PT) was investigated. After pretreatment with PT (1-1000 ng/ml), AVP-stimulated cAMP was not inhibited by NE. The alpha 1 agonist, phenylephrine, fails to inhibit AC or to increase cytosolic Ca in these cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic control of cAMP generation in rat inner medullary collecting tubule cells. 256 11


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