scholarly journals Investigation of the 5-hydroxytryptamine receptor mechanism mediating the short-circuit current response in rat colon

1991 ◽  
Vol 102 (4) ◽  
pp. 811-816 ◽  
Author(s):  
K.T. Bunce ◽  
C.J. Elswood ◽  
M.T. Ball
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Rat Colon ◽  
Current Response

Flupirtine enhances NHE-3 mediated Na+ absorption in rat colon via an ENS-dependent mechanism

2021 ◽  
Author(s):  
Andrew J. Nickerson ◽  
Vazhaikkurichi M. Rajendran
Keyword(s):  
Immunofluorescence Microscopy ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Proximal Colon ◽  
Selective Inhibitor ◽  
Rat Colon ◽  
Pre Treatment ◽  
Apical Membranes ◽  
Microscopy Techniques ◽  
Dependent Mechanism

Recent studies in our lab have shown that the KV7 channel activator, flupirtine, inhibits colonic epithelial Cl- secretion through effects on submucosal neurons of the enteric nervous system (ENS). We hypothesized that flupirtine would also stimulate Na+ absorption as a result of reduced secretory ENS input to the epithelium. To test this hypothesis, unidirectional 22Na+ fluxes were measured under voltage-clamped conditions. Pharmacological approaches using an Ussing-style recording chamber, combined immunofluorescence microscopy techniques were used to determine the effect of flupirtine on active Na+ transport in the rat colon. Flupirtine stimulated electroneutral Na+ absorption in partially seromuscular stripped colonic tissues, while simultaneously inhibiting short circuit current (ISC; i.e., Cl- secretion). Both of these effects were attenuated by pre-treatment with the ENS inhibitor, tetrodotoxin. The NHE-3-selective inhibitor, S3226, significantly inhibited flupirtine-stimulated Na+ absorption whereas the NHE-2-selective inhibitor HOE-694 did not. NHE-3 localization near the apical membranes of surface epithelial cells was also more apparent in flupirtine-treated colon versus control. Flupirtine did not alter epithelial Na+ channel (ENaC)-mediated Na+ absorption in distal colonic tissues obtained from hyperaldosteronaemic rats and had no effect in the normal ileum, but did stimulate Na+ absorption in the proximal colon. Finally, the parallel effects of flupirtine on ISC (Cl- secretion) and Na+ absorption were significantly correlated with each other. Together, these data indicate that flupirtine stimulates NHE-3-dependent Na+ absorption, likely as a result of reduced stimulatory input to the colonic epithelium by submucosal ENS neurons.

Antisecretory effect of prostaglandin D2 in rat colon in vitro: action sites

1991 ◽  
Vol 260 (6) ◽  
pp. G904-G910 ◽  
Author(s):  
K. J. Goerg ◽  
C. Diener ◽  
M. Diener ◽  
W. Rummel
Keyword(s):  
Short Circuit ◽  
Ussing Chamber ◽  
Short Circuit Current ◽  
Rat Colon ◽  
Prostaglandin D2 ◽  
Cyclic Monophosphate ◽  
Heat Stable ◽  
Antisecretory Effect ◽  
Flux Measurements

The effect of prostaglandin D2 (PGD2) on colonic ion transport was studied in the Ussing chamber. PGD2 (10(-6) M) decreased baseline short-circuit current (Isc) in two preparations of rat colon descendens, a mucosa-submucosa preparation with and a mucosa preparation without the submucosal plexus. In both preparations, PGD2 inhibited the neuronally mediated secretory responses to electric field stimulation, the sea anemone toxin ATX II, and different cholinergic agents. Unidirectional flux measurements revealed that PGD2 diminished the secretagogue-induced increase in the serosal-to-mucosal flux of Cl- and thereby inhibited net Cl- secretion. PGD2, however, had no effect on the adenosine 3',5'-cyclic monophosphate-mediated response to forskolin or vasoactive intestinal peptide or on guanosine 3',5'-cyclic monophosphate-mediated secretion induced by the heat-stable enterotoxin of Escherichia coli. The PGD2 also blocked the increase in Isc evoked by two neuronally acting inflammatory mediators, i.e., bradykinin and PGI2 in the mucosa-submucosa preparation, but had no effect on the response to PGE2. Consequently, PGD2 exerts an indirect antisecretory effect caused by an inhibition of enteric secretomotor neurons of both the submucosal and the mucosal plexus.

Effect of the thiol-oxidizing agent diamide on NH2Cl-induced rat colonic electrolyte secretion

1993 ◽  
Vol 265 (1) ◽  
pp. C166-C170 ◽  
Author(s):  
H. Tamai ◽  
J. F. Kachur ◽  
M. B. Grisham ◽  
M. W. Musch ◽  
E. B. Chang ◽  
...  
Keyword(s):  
Colonic Mucosa ◽  
Short Circuit ◽  
Chloride Ion ◽  
Short Circuit Current ◽  
Rat Colon ◽  
Maximal Effect ◽  
Oxidizing Agent ◽  
Maximal Increase ◽  
Ussing Chambers ◽  
Electrolyte Secretion

The granulocyte-derived oxidant, monochloramine (NH2Cl), is known to stimulate chloride ion secretion in rat distal colonic mucosa mounted in Ussing chambers, through mechanisms that are sensitive and insensitive to tetrodotoxin (TTX). The possible role of intracellular thiols, in the mechanism of action of NH2Cl as a secretagogue, was evaluated with the thiol-oxidizing agent diamide and by measuring tissue sulfhydryl levels in response to NH2Cl. Serosal exposure to the antioxidant glutathione (0.25 mM), 5 min before NH2Cl (50 microM) addition, decreased the maximal effect of 50 microM NH2Cl on short-circuit current (Isc). The NH2Cl-stimulated increase in Isc was not affected by mucosal amiloride (5 microM). Pretreatment with 0.1 mM diamide shortened the lag period before the increase in Isc in response to NH2Cl, but it did not affect the maximal increase in Isc. Although TTX (0.5 microM) increased the lag time for achievement of the maximal Isc response to NH2Cl, the neurotoxin did not inhibit the effect of diamide, suggesting that diamide acts primarily on the nonneural component of NH2Cl-stimulated secretion. Incubation of colonic mucosa with NH2Cl, with or without diamide, decreased cellular acid-soluble sulfhydryl concentrations. Taken together, the results support a role for epithelial cell thiols in NH2Cl-stimulated electrolyte secretion by the rat colon.

H+ current response to CO2 and carbonic anhydrase inhibition in turtle bladder

1976 ◽  
Vol 231 (2) ◽  
pp. 565-572 ◽  
Author(s):  
JH Schwartz
Keyword(s):  
Carbonic Anhydrase ◽  
Maximum Rate ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Current Response ◽  
Low Concentrations ◽  
Ph Stat ◽  
High Concentrations ◽  
Co2 Addition

To evaluate the role of CO2 and carbonic anhydrase (CA) in H+ transport (JH) by turtle urinary bladder the effect of CO2 addition, with and without addition of CA inhibitiors, was examined on JH. Since in the presence of exogenous CO2 and HCO3- the pH stat-measured rate of mucosal (M) acidification underestimates JH by the rate of electroneutral HCO3- secretion, the reverse short-circuit current (RSCC) applied across ouabain-treated bladders was used to estimate JH. That the RSCC is a measure of JH was demonstrated by: 1) in the absence of added CO2 and HCO3- the rate of M acidification totally accounted for the RSCC, and 2) increases in RSCC with CO2 addition occurred without changes in Na+ and K+ fluxes or the coupled ration of HCO3- secretion for Cl-absorption. When serosal (S) percent CO2 was progressively progressively increased JH achieved a maximum rate of 64 +/- 3 muA (SE) with 4.5% CO2. At higher S percent CO2 JH did not change, suggesting that factors other than the rate of CO2 hydration were rate limiting. The maximum rate of JH was not decreased by low concentrations of CA inhibitors (acetazolamide, 5 X 10(-5) M), although the percent CO2 at which this maximum rate occurred increased to 8.5%. The increased percent CO2 requirement for the maximum rate of JH with low concentrations of CA inhibitors suggests that these agents alter JH by decreasing the rate of enzymatic CO2 hydration. At high concentrations (acetazolamide, 5 X 10(-4) M) these inhibitors decrease the maximum rate of JH in the presence of CO2, implying that these inhibitors at higher concentrations directly interfere with the H+ transport system.

INTERRELATIONSHIP OF THE EFFECTS OF ALDOSTERONE AND THYROID HORMONES ON SODIUM TRANSPORT AND ELECTRICAL PROPERTIES OF RAT COLON

1970 ◽  
Vol 48 (2) ◽  
pp. 189-197 ◽  
Author(s):  
C. J. EDMONDS ◽  
B. D. THOMPSON ◽  
JANE MARRIOTT
Keyword(s):  
Body Weight ◽  
Electrical Resistance ◽  
Actinomycin D ◽  
Short Circuit ◽  
Electrical Potential ◽  
Short Circuit Current ◽  
Rat Colon ◽  
Electrical Potential Difference ◽  
Influx Rate ◽  
Descending Colon

SUMMARY Transmucosal electrical potential difference (p.d.), short-circuit current, electrical resistance and Na+ influx rate of the descending colon were similar in euthyroid and hypothyroid rats, the latter having been treated earlier with an ablation dose of 131I. However, in contrast to the considerable p.d. increase found in normal rats, little change of p.d. was found in hypothyroid rats when they were Na+ depleted or given an intravenous aldosterone infusion. A single small dose of tri-iodothyronine (T3) (1 μg/100g body weight) or a larger dose of thyroxine given to hypothyroid rats 10–16 h before aldosterone, restored the p.d. response to normal, although these doses did not influence the animal's oxygen consumption. Fasting for 3 days or giving actinomycin D (8 μg/100 g body weight) abolished the effect of T3 but this did not influence the action of aldosterone in euthyroid animals.

Colitis reduces short-circuit current response to inflammatory mediators in rat colonic mucosa

Inflammation ◽  
1995 ◽  
Vol 19 (2) ◽  
pp. 245-259 ◽  
Author(s):  
J. F. Kachur ◽  
A. Keshavarzian ◽  
R. Sundaresan ◽  
M. Doria ◽  
R. Walsh ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Colonic Mucosa ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Current Response

Regulation of amiloride-sensitive electrogenic sodium transport in the rat colon by steroid hormones

1985 ◽  
Vol 248 (1) ◽  
pp. G124-G132 ◽  
Author(s):  
P. C. Will ◽  
R. N. Cortright ◽  
R. C. DeLisle ◽  
J. G. Douglas ◽  
U. Hopfer
Keyword(s):  
Sodium Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Serum Levels ◽  
Rat Colon ◽  
Sodium Absorption ◽  
Sodium Deficiency ◽  
Synthetic Glucocorticoids

The role of steroids in the regulation of colonic sodium transport was examined by infusing steroids into adrenalectomized (ADX) rats and evaluating the short-circuit current (ISC) in vitro. Amiloride-sensitive ISC was induced by aldosterone and corticosterone with half-maximal doses (ED50) of 2 and 260 micrograms X kg-1 X h-1), respectively. Synthetic glucocorticoids such as methylprednisolone (33 mg/kg) and dexamethasone (ED50 = 30 micrograms X kg-1 X h-1) were also effective. Supramaximal doses of aldosterone (7.5 times ED50) for 24 h increased the total ISC (7-fold), the amiloride-sensitive ISC (366-fold), and the conductance (2-fold), as well as the potassium-stimulated phosphatase activity (2-fold) (reported previously). Compared with aldosterone, supramaximal doses of dexamethasone (4 times ED50) produced greater increases in the total ISC (15-fold) and the amiloride-sensitive ISC (674-fold). In contrast to aldosterone, dexamethasone also increased the amiloride-insensitive ISC (3-fold). Glucocorticoid action was not mediated by insulin since the ISC from diabetic ADX rats was increased by dexamethasone to a similar extent (11-fold) as in nondiabetic rats. Estradiol, progesterone, and testosterone did not stimulate the colonic ISC of ADX rats. The ED50 values of corticosterone and aldosterone, measured in terms of amiloride-sensitive sodium transport, produced serum levels that were slightly above those of unstressed, adrenal-intact animals and thus must be considered physiological. It is concluded that at physiological levels both steroids may mediate amiloride-sensitive sodium transport in the rat colon. However, as judged from changes in serum steroid levels, aldosterone is the physiological regulator of elevated sodium absorption in sodium deficiency.

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