Inhibition of adenylate cyclase by general anesthetics in toad urinary bladder

Levine, Sherman D.; Weber, Heather W.; Schlöndorff, Detlef

doi:10.1152/ajprenal.1979.237.5.f372

Cited by 9 publications

(9 citation statements)

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“…Moreover, both the low sucrose permeability and high transepithelial electrical resistance suggest that the paracellular barriers to solute transport remain intact. In accord with our previous work, this demonstrates the independence ofthe water, sodium, and urea pathways (5,7,17).…”

Section: Discussionsupporting

confidence: 92%

“…Hydrazine, on the other hand, enhances vasopressin-stimulation of water flow, stimulates cyclase, and increases the protein kinase activity ratio. Neither ofthese agents alters the water flow response to exogenous cAMP (5,17). In contrast, trifluoperazine inhibited vasopressin-stimulated water flow but did not alter the intracellular cAMP increment associated with vasopressin administration.…”

Section: Discussionmentioning

confidence: 94%

“…After a 2-min centrifugation in a clinical centrifuge, the cells were suspended in 5 mM Tris, 5 mM NaCl, pH 7.4, and homogenized by 18-20 strokes with a tight Dounce homogenizer. After an additional 2 min centrifugation to remove unhomogenized tissue, the supernate was collected and cyclic AMP phosphodiesterase activity measured according to the method of Rangel-Aldao et al (16) as reported (17). The reaction mixture consisted of 40 mM Tris, pH 8.0, 10 mM MgC12, 2 mM dithiothreitol, 1 mg/ml bovine serum albumin, 0.5 ,.tM [3H]cyclic AMP (New England Nuclear) (40,000-60,000 cpm/assay).…”

Section: Methodsmentioning

confidence: 99%

“…Hydrolysis of cyclic AMP proceeded linearly over the period oftime and protein concentrations used. Phosphodiesterase activity in the homogenate follows Michaelis-Menten kinetics with a single Km of about 3 ,uM over a cyclic AMP concentration of 0.5 to 100 ,uM (17). All determinations were performed in duplicate.…”

Section: Methodsmentioning

confidence: 99%

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Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability.

Levine¹,

Kachadorian²,

Levin³

et al. 1981

J. Clin. Invest.

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A B S T R A C T Calcium ion plays a major regulatory role in many hormone-stimulated systems. To determine the site of calcium's action in the toad urinary bladder, we examined the effect of trifluoperazine, a compound that binds specifically to the calcium binding protein, calmodulin, and thereby prevents activation of enzymes by the calcium-calmodulin complex. 10 ,LM trifluoperazine inhibited vasopressin stimulation of water flow, but did not alter vasopressin's effects on urea permeability or short-circuit current. Trifluoperazine also blocked stimulation of water flow by cyclic AMP and methylisobutylxanthine, implying a "postcyclic AMP" site of action. Consistent with these results, trifluoperazine did not decrease epithelial cyclic AMP content or the cyclic AMP-dependent protein kinase activity ratio. Assay of bladder epithelial supernate demonstrated calmodulin-like activity of 1.5 U/lg protein. Morphologic studies of vasopressintreated bladders revealed that trifluoperazine did not alter the volume density of cytoplasmic microtubules or significantly decrease the number of fusions between cytoplasmic, aggregate-containing, elongated vesicles and the luminal membrane. Nonetheless, the frequency of luminal membrane aggregates, structures that correlate well with luminal membrane water permeability, was decreased by >50%. Thus, trifluoperazine appears to inhibit the movement of intramembranous particle aggregates from the fused intracellular membranes to the luminal membrane, perhaps by blocking an effect ofcalcium on microfilament function.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability.

Levine¹,

Kachadorian²,

Levin³

et al. 1981

J. Clin. Invest.

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“…5) can be partially explained in the light of current views concerning the multicomponent structure of adenylate cyclase (Gilman, 1984). According to Levine, Weber & Schlondorff (1979), methohexital inhibits adenylate cyclase at a step beyond the V2 receptor that triggers the hydrosmotic response. Consistent with this hypothesis is the observation that methohexital also inhibits vasopressin when added to the solution bathing the outer surface of toad bladder .…”

Section: Dissimilarity Of Vasopressin and Forskolin Hydrosmotic Actionsmentioning

confidence: 99%

Forskolin mimics the hydrosmotic action of vasopressin in the urinary bladder of toads Bufo marinus.

Sousa¹,

Grosso²

1985

The Journal of Physiology

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(trifluoperazine, vanadate, silver, cobalt, manganese and Ca2+-free Ringer solution) of the vasopressin response, induced parallel changes in the forskolin response.5. Three agents, however, induced dissimilar effects on vasopressin and forskolin: high K+ potentiated vasopressin but inhibited forskolin; methohexital and diamide inhibited vasopressin but had no effect on forskolin.6. The forskolin-induced hydrosmotic response can be viewed as a new criterion for ascertaining the messenger role of cycle AMP in the the hydrosmotic effect of vasopressin.

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Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates?

Natochin

Firsov

et al. 1992

Pflugers Arch.

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In experiments on frog urinary bladder the mechanisms behind the gradual development of a hydroosmotic reaction to antidiuretic hormone (ADH) were investigated. It was suggested that the velocity of hydroosmotic reaction may be limited by (a) formation and insertion of particle aggregates into the apical membrane or (b) by velocity of cAMP formation. The urinary bladders were exposed to 23 nM ADH for different times (from 1 to 20 min) and water flow was measured over a period of 40 min. It was found that the value of the full hydroosmotic response increased progressively with the time of exposure to the hormone; however, the enhancement of water flow was equal during each time interval before reaching the reaction maximum. A direct correlation between the value of ADH-stimulated water flow, cAMP content in bladder tissue and frequency of particle aggregates in the granular cell apical membrane was observed. The content of cAMP in ADH-treated bladders was higher by 80% in the absence than in the presence of an osmotic gradient. Pretreatment of urinary bladders with 50 microM cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, significantly accelerated the development of the hydroosmotic reaction and increased the magnitude of water flow in comparison with the effect of ADH only. No changes in cyclic AMP phosphodiesterase activity were found in the urinary bladder homogenates under the action of ADH, so it seems likely that accumulation of cAMP depends only on the increase of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

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Inhibition of adenylate cyclase by general anesthetics in toad urinary bladder

Cited by 9 publications

References 0 publications

Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability.

Effects of trifluoperazine on function and structure of toad urinary bladder. Role of calmodulin vasopressin-stimulation of water permeability.

Forskolin mimics the hydrosmotic action of vasopressin in the urinary bladder of toads Bufo marinus.

Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates?

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