Protein Information

Name adenylate cyclase
Synonyms AH related protein; HCA2; ATP pyrophosphate lyase; Adenylate cyclase; Adenylyl cyclase soluble; HCA 2; RP1 313L4.2; SAC…

Compound Information

Name diphenylamine
CAS

Reference List

PubMed Abstract RScore(About this table)
9218212 Chan HC, Fong SK, So SC, Chung YW, Wong PY: Stimulation of anion secretion by beta-adrenoceptors in the mouse endometrial epithelium. J Physiol. 1997 Jun 15;501 ( Pt 3):517-25.

The effect of adrenaline on the ISC was mimicked by an adenylate cyclase activator, forskolin, but suppressed by the adenylate cyclase inhibitor MDL 12,330A, indicating the involvement of cAMP. 7.
The adrenaline-induced ISC could be inhibited by pretreatment with diphenylamine 2,2'-dicarboxylic acid (DPC) or replacement of external Cl- and HCO3-, but not by amiloride or replacement of Na+ in apical solution. 3.
1(0,0,0,1) Details
10381142 Panesar NS: Role of chloride and inhibitory action of inorganic nitrate on gonadotropin-stimulated steroidogenesis in mouse Leydig tumor cells. Metabolism. 1999 Jun;48(6):693-700.

The involvement of adenylate cyclase-cyclic adenosine monophosphate (AC-cAMP) in gonadotropin-stimulated testicular steroidogenesis is well known.
A chloride-channel inhibitor, diphenylamine-2-carboxylate (DPC), at concentrations up to 0.6 mmol/L stimulated basal steroid secretion and hCG 10 IU/L stimulated cAMP production, but higher concentrations had an inhibitory effect.
1(0,0,0,1) Details
10611078 Leung GP, Wong PY: Activation of cystic fibrosis transmembrane conductance regulator in rat epididymal epithelium by genistein. Biol Reprod. 2000 Jan;62(1):143-9.

The response could be blocked by the nonspecific Cl (-) channel blocker, diphenylamine-2-carboxylate (DPC), but not by the Ca (2+)-activated Cl (-) channel blocker, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS).
Moreover, pretreatment of the tissues with MDL-12330A, an adenylate cyclase inhibitor, markedly attenuated the Isc response to genistein, but the response was restored upon the addition of exogenous cAMP.
1(0,0,0,1) Details
16760378 Du JY, Ruan YC, Zuo WL, Yang ZH, Chen MH, Wu ZL, Xiang H, Zhou WL: Cellular mechanisms of carbachol-stimulated Cl- secretion in rat epididymal epithelium. Biol Reprod. 2006 Sep;75(3):407-13. Epub 2006 Jun 7.

Ca2+ activated Cl- channel blocker disulfonic acid stilbene (DIDS, 300 microM) only inhibited part of the CCH-induced Isc response, while nonselective Cl- channel blocker diphenylamine-dicarboxylic acid (DPC, 1 mM) reduced all, indicating the involvement of different conductance pathways.
Both peaks of the CCH-induced Isc response could be significantly inhibited by pretreatment with an adenylate cyclase inhibitor, MDL12330A (50 microM).
1(0,0,0,1) Details
16015685 He Q, Zhu JX, Xing Y, Tsang LL, Yang N, Rowlands DK, Chung YW, Chan HC: Tetramethylpyrazine stimulates cystic fibrosis transmembrane conductance regulator-mediated anion secretion in distal colon of rodents. World J Gastroenterol. 2005 Jul 21;11(27):4173-9.

RESULTS: TMP stimulated a concentration-dependent rise in I (SC), which was dependent on both Cl (-) and HCO (3)(-), and inhibited by apical application of diphenylamine-2,2'-dicarboxylic acid (DPC) and glibenclamide, but resistant to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate (DIDS).
RIA results showed that TMP (1 mmol/L) elicited a significant increase in cellular cAMP production, which was similar to that elicited by the adenylate cyclase activator, forskolin (10 micromol/L).
1(0,0,0,1) Details
16038730 Assef YA, Cavarra SM, Damiano AE, Ibarra C, Kotsias BA: Ionic currents in multidrug resistant K562 human leukemic cells. Leuk Res. 2005 Sep;29(9):1039-47. Epub 2005 Apr 19.

Forskolin (40 microM n activator of adenylate cyclase, added to the extracellular side increased the current in both cell lines.
A fraction of the activated whole cell currents was inhibited by 500 microM 4,4-diisothiocyanatostilbene-2,2-disulfonic acid (DIDS) and subsequent addition of 500 microM diphenylamine-2-carboxylate (DPC plus DIDS) further inhibited the remaining currents.
1(0,0,0,1) Details
9224546 Saidane D, Lahlou B, Tritar B: Regional variations in electrical and ion transport properties along the isolated intestine of the frog Rana esculenta. Arch Physiol Biochem. 1997 Feb;105(1):45-52.

Na+/K+/2Cl- cotransport (current decreased by about 50% by bumetanide in anterior and posterior regions only), Cl- permeability or channels inhibited by diphenylamine-2-carboxylate, DPC (similar decreases as by bumetanide).
Finally, current increase by IBMX and theophylline designate the colon as a target for adenylate cyclase stimulating hormones.
1(0,0,0,1) Details
8743460 Sullivan LP, Grantham JJ: Mechanisms of fluid secretion by polycystic epithelia. Kidney Int. 1996 Jun;49(6):1586-91.


These preparations absorb fluid in the control state but secrete fluid in response to native cyst fluid, to adenylate cyclase agonists and to permeant analogues of cAMP.
1(0,0,0,1) Details
8447435 Siga E, Mandon B, Roinel N, de Rouffignac C: Effects of calcitonin on function of intercalated cells of rat cortical collecting duct. Am J Physiol. 1993 Feb;264(2 Pt 2):F221-7.

In the rat cortical collecting duct (CCD), the presence of highly specific receptors to calcitonin (CT) coupled to a sensitive adenylate cyclase system suggests that this segment is a target site for CT.
The CT-induced lumen-positive PDte was reduced by 2.3 +/- 0.8 mV after the basolateral addition of the Cl- channel inhibitor diphenylamine-2-carboxylate. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and acetazolamide, which inhibit Cl-/HCO3- exchangers and carbonic anhydrase activities, respectively, also inhibited the CT-induced PDte by 4.6 +/- 0.5 and 5.0 +/- 0.9 mV.
1(0,0,0,1) Details
9379115 Zhou WL, Leung PS, Wong TP, Dun NJ, Wong PY, Chan HC: Local regulation of epididymal anion secretion by pituitary adenylate cyclase-activating polypeptide. J Endocrinol. 1997 Sep;154(3):389-95.

The Isc response to PACAP38 was abolished in Cl-(-) free solution and completely inhibited by the Cl- channel blocker, diphenylamine-dicarboxylic acid.
The Isc response to PACAP38 was also suppressed by pretreatment of the cells with the adenylate cyclase inhibitor, MDL12330A.
1(0,0,0,1) Details
18784353 Du JY, Zuo WL, Ruan YC, Yang ZH, Chen MH, Chen SL, Li S, Wu ZL, Xiang H, Zhou WL: Stimulating effects of dopamine on chloride transport across the rat caudal epididymal epithelium in culture. Biol Reprod. 2009 Jan;80(1):13-23. Epub 2008 Sep 10.

The response was inhibited by the apical Cl- channel blocker, diphenylamine-dicarboxylic acid, and the Ca2+-activated Cl- channel blocker, disulfonic acid stilbene, indicating that Cl- may pass through two types of Cl- channels on the apical side.
Pretreating the monolayers with an adenylate cyclase inhibitor, MDL12330A, inhibited all of the second Isc response and part of the initial spike.
1(0,0,0,1) Details
2411931 Cuthbert AW, Hickman ME: Indirect effects of adenosine triphosphate on chloride secretion in mammalian colon. J Membr Biol. 1985;86(2):157-66.


Using inhibitors of NaCl cotransport (piretanide), carbonic anhydrase (acetazolamide), and chloride channels (diphenylamine-2-carboxylate), it was concluded that the SCC response to ATP was due to chloride secretion with, perhaps, a minor contribution from bicarbonate.
0(0,0,0,0) Details
12181292 Cowley EA, Linsdell P: Oxidant stress stimulates anion secretion from the human airway epithelial cell line Calu-3: implications for cystic fibrosis lung disease. J Physiol. 2002 Aug 15;543(Pt 1):201-9.


This increase was almost entirely abolished by the addition of diphenylamine-2-carboxylate (DPC), implicating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel in the response.
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9546734 Fong SK, Chan HC: Regulation of anion secretion by prostaglandin E2 in the mouse endometrial epithelium. Biol Reprod. 1998 Apr;58(4):1020-5.

Pretreatment with diphenylamine 2,2'-dicarboxylic acid, a Cl- channel blocker, significantly reduced both PGE2-induced ISC responses, while pretreatment with amiloride, a Na+ channel blocker, did not exert any effect.
Forskolin, an adenylate cyclase activator, and 3-isobutyl-dihydro-testosterone-1-methyl-xanthine, a cAMP phosphodiesterase inhibitor, mimicked the ISC response to PGE2 while MDL12330A, an adenylate cyclase inhibitor, completely abolished the PGE2-induced ISC.
1(0,0,0,1) Details
14715281 Mahlangu DA, Dix JA: Halide fluxes in epithelial cells measured with an automated cell plate reader. Anal Biochem. 2004 Feb 1;325(1):28-34.

Isoproterenol (a modulator of cAMP-activated chloride channels) increased the exchange rate by a factor of 1.4+/-0.1; A23187 (a modulator of calcium-activated chloride channels) increased the rate by 3.4+/-0.4; bradykinin (also a modulator of calcium-activated chloride channels) increased the rate by 2.0+/-0.4; forskolin (a direct stimulator of adenylate cyclase) increased the rate by 2.7+/-0.3.
Diphenylamine-2-carboxylate (a chloride channel blocker) decreased the rate by 0.12+/-0.03.
1(0,0,0,1) Details
1708205 Heisler S: Chloride channel blockers inhibit ACTH secretion from mouse pituitary tumor cells. Am J Physiol. 1991 Apr;260(4 Pt 1):E505-12.

When cells were simultaneously exposed to diphenylamine-2-carboxylate (DPC) or related substances (Hoechst compounds 131, 143, and 144) and the adenylate cyclase activator forskolin, ACTH secretion was inhibited by 76-95% [half-maximal inhibitory concentration (IC50) 450, 15, 84, and 32 microM, respectively].
32(0,1,1,2) Details
8807590 Davidow CJ, Maser RL, Rome LA, Calvet JP, Grantham JJ: The cystic fibrosis transmembrane conductance regulator mediates transepithelial fluid secretion by human autosomal dominant polycystic kidney disease epithelium in vitro. Kidney Int. 1996 Jul;50(1):208-18.

We now report that forskolin, which stimulates adenylate cyclase, increased the efflux rate constant for 36Cl in monolayers of ADPKD cells in vitro from 0.23 +/- 0.02 min-1 to 0.44 +/- 0.05 min-1 (N = 4) and that diphenylamine 2-carboxylate (DPC), which blocks chloride channels, eliminated the forskolin-stimulated chloride efflux from these cells.
31(0,1,1,1) Details
9916004 Chan LN, Chung YW, Leung PS, Liu CQ, Chan HC: Activation of an adenosine 3',5'-cyclic monophosphate-dependent Cl- conductance in response to neurohormonal stimuli in mouse endometrial epithelial cells: the role of cystic fibrosis transmembrane conductance regulator. Biol Reprod. 1999 Feb;60(2):374-80.

The agonist-activated current could be mimicked by an adenylate cyclase activator, forskolin (10 microM), and suppressed by an adenylate cyclase inhibitor, MDL12330A, suggesting the involvement of cAMP.
The agonist-induced current was inhibited by the Cl- channel blocker diphenylamine 2,2'-dicarboxylic acid (DPC), but not by the Cl- channel blocker 4,4'-diisothiocyanatostibene-2, 2'-disulfonic acid (DIDS).
1(0,0,0,1) Details
9627094 Chan HC, Lui KM, Wong WS, Poon AM: Effect of melatonin on chloride secretion by human colonic T84 cells. Life Sci. 1998;62(23):2151-8.

The increase in I (SC) was also blocked by apical addition of two Cl- channel blockers, 4,4'-diisothiocyanatostibene-2,2'-disulfonic acid (DIDS) and diphenylamine-2-carboxylic acid (DPC), indicating that melatonin stimulated Cl- secretion.
However, inhibitors for Gi-protein, adenylate cyclase or phospholipase C were found to be ineffective in inhibiting the melatonin-induced I (SC).
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2821159 Reuss L: Cyclic AMP inhibits Cl-/HCO3- exchange at the apical membrane of Necturus gallbladder epithelium. J Gen Physiol. 1987 Aug;90(2):173-96.

Intracellular cAMP levels were raised by addition of either the phosphodiesterase inhibitor theophylline (3 X 10 (-3) M) or the adenylate cyclase activator forskolin (10 (-5) M) to the serosal bathing solution.
Estimates of the conductive flux, obtained by either reducing simultaneously mucosal [Cl-] and [HCO3-] or lowering [Cl-] alone in the presence of a blocker of anion exchange (diphenylamine-2-carboxylate), indicate that elevation of intracellular cAMP inhibited the anion exchanger by approximately 50%.
1(0,0,0,1) Details