Intestinal mucosal cyclic GMP: regulation and relation to ion transport

1976 ◽  
Vol 231 (1) ◽  
pp. 275-282 ◽  
Author(s):  
TA Brasitus ◽  
M Field ◽  
DV Kimberg
Keyword(s):  
Causal Relationship ◽  
Cyclic Gmp ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Ileal Mucosa ◽  
Muscarinic Cholinergic Receptors ◽  
Cholecystokinin Octapeptide ◽  
Muscarinic Cholinergic ◽  
Stimulation Of

Stimulation of alpha-adrenergic and muscarinic cholinergic receptors in rabbit ileal mucosa in vitro produced 5- to 15-fold increases in cyclic GMP (cGMP) concentration that were maximal within 2 min and gone within 30 min. Cholecystokinin octapeptide and insulin caused similar increases in cGMP. None of these agents affected cAMP. The epinephrine-induced increase in cGMP was blocked by atropine at 100 but not at 1 muM concentration. Epinephrine stimulates active NaCl absorption and decreases short-circuit current (SCC) in vitro, the latter effect due to inhibition of HCO3 secretion. Atropine (100 muM) blocked the former but not the latter effect of epinephrine. In vitro additions of several concentrations of cGMP and 8-bromo-cGMP did not decrease SCC or alter Na fluxes. Thus, changes in cGMP concentration have been directly correlated with changes in active absorption of NaCl, but a causal relationship has not been proven.

An Investigation of the Role of Possible Neural Mechanisms in Cholera Toxin-Induced Secretion in Rabbit Ileal Mucosa in Vitro

1989 ◽  
Vol 77 (2) ◽  
pp. 161-166 ◽  
Author(s):  
K. J. Moriarty ◽  
N. B. Higgs ◽  
M. Woodford ◽  
L. A. Turnberg
Keyword(s):  
Cholera Toxin ◽  
Fluid Transport ◽  
Short Circuit ◽  
Electrical Potential ◽  
Short Circuit Current ◽  
Electrical Potential Difference ◽  
Rabbit Ileum ◽  
Ileal Mucosa

1. Cholera toxin stimulates intestinal secretion in vitro by activation of mucosal adenylate cyclase. However, it has been proposed that cholera toxin promotes secretion in vivo mainly through an indirect mechanism involving enteric neural reflexes. 2. We examined this hypothesis further by studying the influence of neuronal blockade on cholera toxin-induced changes in fluid transport across rabbit ileum in vitro. Mucosa, stripped of muscle layers, was mounted in flux chambers and luminal application of crude cholera toxin (2 μg/ml) caused a delayed but sustained rise in the short-circuit current, electrical potential difference and Cl− secretion. Pretreatment with the nerve-blocking drug, tetrodotoxin (5 × 10−6 mol/l serosal side), failed to influence the secretory response to cholera toxin, and addition of tetrodotoxin at the peak response to cholera toxin also had no effect. 3. That tetrodotoxin could block neurally mediated secretagogues was confirmed by the demonstration that the electrical responses to neurotensin (10−7 mol/l and 10−8 mol/l) were blocked by tetrodotoxin (5 × 10−6 mol/l). Furthermore, the response to cholera toxin of segments of ileum, which included the myenteric, submucosal and mucosal nerve plexuses, was not inhibited by tetrodotoxin. 4. We conclude that cholera toxin-induced secretion in rabbit ileum in vitro is not mediated via a neurological mechanism.

Chronic regulation of transepithelial Na+ transport by the rate of apical Na+ entry

1996 ◽  
Vol 270 (2) ◽  
pp. C600-C607 ◽  
Author(s):  
M. D. Rokaw ◽  
E. Sarac ◽  
E. Lechman ◽  
M. West ◽  
J. Angeski ◽  
...  
Keyword(s):  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Maximal Activity ◽  
Na Channels ◽  
Na Transport ◽  
Bottom Structures ◽  
Stimulation Of

In several settings in vivo, prolonged inhibition of apical Na+ entry reduces and prolonged stimulation of apical entry enhances the ability of renal epithelial cells to reabsorb Na+, an important feature of the load-dependent regulation of renal tubular Na+ transport. To model this load dependency, apical Na+ entry was inhibited or stimulated for 18 h in A6 cells and vectorial transport was measured as short-circuit current (Isc) across monolayers on filter-bottom structures. Basal amiloride-sensitive Isc represents the activity of apical Na+ channels, whereas Isc after permeabilization of the apical membrane to cations with nystatin represents maximal activity of the basolateral Na(+)-K(+)-ATPase. Chronic inhibition of apical Na+ entry by 18-h apical exposure to amiloride or replacement of apical Na+ with tetramethylammonium (TMA+), followed by washing and restoration of normal apical medium, revealed a persistent decrease in Isc that remained despite exposure to nystatin. Both basal and nystatin-stimulated Isc recovered progressively after restoration of normal apical medium. In contrast, chronic stimulation of apical Na+ entry by short circuiting the epithelium increased Isc in the absence and presence of nystatin, indicating upregulation of both apical Na+ channels and basolateral Na(+)-K(+)-ATPase. Basolateral equilibrium [3H]ouabain binding was reduced to 67 +/- 5% in TMA+ vs. control cells, whereas values in 18-h short-circuited cells increased by 42 +/- 19%. The results demonstrate that load dependency of tubular Na+ transport can be modeled in vitro and indicate that the regulation of Na(+)-K(+)-ATPase observed in these studies occurs in part by changes in the density of functional transporter proteins within the basolateral membrane.

Effects of somatostatin on intestinal calcium transport in the rat

1981 ◽  
Vol 241 (3) ◽  
pp. G215-G221
Author(s):  
M. J. Favus ◽  
M. Berelowitz ◽  
F. L. Coe
Keyword(s):  
Tissue Concentration ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Strongly Correlated ◽  
Dihydroxyvitamin D3 ◽  
Intestinal Segments ◽  
Absorptive Flux ◽  
Calcium Secretion ◽  
Stimulation Of

The addition of somatostatin (SRIF) to rat descending colon in vitro increased the calcium secretory flux from serosa to mucosa (Js leads to m) and reduced tissue short-circuit current (Isc) but did not alter the absorptive flux from mucosa to serosa (Js leads to m). Js leads to m increased by 37% at 10(-9) M SRIF and by 48% at 10(-6) M. The response to SRIF was not altered by 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], and SRIF did not interfere with stimulation of calcium Jm leads to s by 1,25(OH)2D3. Removal of sodium from the buffer abolished the stimulation of Js leads to m by SRIF without reducing basal Js leads to m. Secretory fluxes of mannitol and calcium were strongly correlated in the presence and absence of SRIF, suggesting that SRIF stimulates a paracellular transepithelial pathway for calcium. In the duodenum, SRIF altered neither calcium Js leads to m nor Isc. In the ileum, calcium Js leads to m increased and Isc decreased, as in the colon, but only by 28 and 12%, respectively. The maximal change in calcium Js leads to m caused by SRIF in these three intestinal segments was negatively correlated with the tissue concentration of immunoreactive SRIF. These results suggest that intestinal calcium secretion could, in part, be regulated by intestinal SRIF.

Failure of 16,16-dimethyl PGE2 to prevent inhibitory effect of ethanol on sodium transport in canine gastric mucosa

1985 ◽  
Vol 248 (3) ◽  
pp. G299-G306
Author(s):  
T. A. Miller ◽  
J. M. Henagan ◽  
Y. J. Kuo ◽  
L. L. Shanbour
Keyword(s):  
Gastric Mucosa ◽  
Sodium Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Inhibitory Effect ◽  
Gastric Epithelium ◽  
Bathing Solution ◽  
Inhibitory Effects ◽  
Stimulation Of

By use of an in vitro canine gastric mucosal preparation, we evaluated the effects of ethanol (2, 4, 6, and 8%, vol/vol) and indomethacin (2.2 X 10(-4)M), with and without 16,16-dimethyl PGE2 pretreatment, on net sodium transport (JNanet) (mucosal to serosal) across gastric epithelium. Although administration of 2 or 4% ethanol to the mucosal bathing solution had no appreciable inhibitory effects on sodium transport, 6 and 8% ethanol and indomethacin significantly inhibited JNanet when compared with untreated control mucosa. This effect was accompanied by inhibition of transmucosal potential difference (PD) and short-circuit current (Isc). In other mucosae exposed to dimethyl PGE2 (8 X 10(-6) M) in the serosal bathing solution, significant increases in JNanet, PD, and Isc were noted when compared with control mucosa. Addition of 6 or 8% ethanol to the mucosal solution of dimethyl PGE2-pretreated tissue resulted in significant decreases in PD, Isc, and JNanet below control values that were not significantly different from mucosa exposed to 6 and 8% ethanol without PG pretreatment. When indomethacin was added to the mucosal solution following dimethyl PGE2 pretreatment, only slight decreases in PD and Isc below control levels were observed, and the inhibitory effects on JNanet induced by indomethacin without such treatment were abolished. These findings suggest that stimulation of JNanet by prostaglandin may play a role in its ability to prevent indomethacin damage to gastric epithelium but does not appear to be of importance in mediating protection against ethanol damage.

alpha 2-Adrenergic receptor regulation of ion transport in rabbit ileum

1982 ◽  
Vol 242 (3) ◽  
pp. G237-G242 ◽  
Author(s):  
E. B. Chang ◽  
M. Field ◽  
R. J. Miller
Keyword(s):  
Ion Transport ◽  
Adrenergic Receptor ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Maximal Effect ◽  
Rabbit Ileum ◽  
Ileal Mucosa ◽  
Receptor System ◽  
Alpha Adrenergic Receptors

Catecholamines are known to decrease short-circuit current (Isc), stimulate NaCl absorption, and inhibit HCO3 secretion in rabbit ileal mucosa in vitro. These effects appear to be mediated by alpha-adrenergic receptors because they are partially blocked by phentolamine and not by propranolol. To further characterize this receptor system, we determined the interactions of epinephrine (Epi) with alpha-subtype-selective antagonists. Prazosin (PZ), a specific alpha 1-antagonist, did not alter the Epi dose-response curve at concentrations up to 10(-5) M. Yohimbine (YO), a specific alpha 2-antagonist, completely inhibited the Epi effect on Isc. At 10(-5) M, YO increased by 70-fold the concentration of Epi required to produce a half-maximal effect (ED50; from 1.4 X 10(-7) M to 10(-5) M). YO and PZ by themselves had no significant effect on Isc in concentrations up to 10(-5) M. Clonidine, a specific alpha 2-agonist, decreased Isc with an ED50 similar to that of Epi; its effect was blocked by YO but not by PZ. Two alpha 1-selective agonists, methoxamine and phenylephrine, only caused a decrease in Isc in doses greater than 10(-5) M. This effect was reversed by YO but not by PZ. The effects of YO and PZ on Epi-modified Cl fluxes were also determined. YO completely aborted the effects of Epi on net Cl flux. No significant effects were seen with PZ. We conclude that the effects of Epi on ileal ion transport are mediated by a specific alpha 2-adrenergic receptor present in ileal mucosa and that no physiologic alpha 1-receptor function can be demonstrated.

Altered regulation of intestinal ion transport by enteric nerves in diabetic rats

1988 ◽  
Vol 254 (3) ◽  
pp. G444-G449 ◽  
Author(s):  
M. H. Perdue ◽  
J. S. Davison
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Cholinergic Receptor ◽  
Diabetic Rats ◽  
Muscarinic Agonist ◽  
Transport Parameters ◽  
Ileal Mucosa ◽  
Enteric Nerves ◽  
Muscarinic Cholinergic

We compared ion transport parameters in isolated ileal mucosa from diabetic rats (8 wk after streptozotocin injection) and littermate controls under basal conditions and in response to electrical transmural stimulation (TS). Stripped ileal mucosa (submucosal plexus intact) was mounted in Ussing flux chambers modified to include stimulating electrodes on opposite sides of the tissue. Under basal conditions unidirectional fluxes of Na+ and Cl- were decreased across mucosa from diabetic rats compared with controls, whereas net fluxes were not significantly different. TS caused a tetrodotoxin (TTX)-sensitive transient increase in short-circuit current (Isc) that was significantly less in tissue from diabetic than control rats. The muscarinic cholinergic receptor antagonist, atropine, significantly reduced the Isc response to TS in ileum from control but not diabetic rats. In addition, the noncholinergic component of the response was smaller. The muscarinic agonist, Urecholine chloride (bethanechol chloride), caused an increase in Isc that was unaffected by pretreatment with TTX and was the same in tissue from control and diabetic rats. Our results suggest that the intestinal abnormalities that occur in diabetes may include a defect in the regulation of ion transport by enteric nerves resulting in an abnormal ability to respond to luminal and other stimuli.

Effect of serotonin on active electrolyte transport in rabbit ileum, gallbladder, and colon

1980 ◽  
Vol 239 (6) ◽  
pp. G463-G472 ◽  
Author(s):  
M. Donowitz ◽  
Y. H. Tai ◽  
N. Asarkof
Keyword(s):  
Maximum Concentration ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Electrolyte Transport ◽  
Rabbit Ileum ◽  
Rabbit Gallbladder ◽  
Epithelial Sheets ◽  
Dose Dependent ◽  
Stimulation Of

The effect of serotonin on active electrolyte transport was evaluated in vitro in epithelial sheets of rabbit ileum, gallbladder, and colon under short-circuited conditions. Serotonin added to the serosal surface of rabbit ileum caused a dose-dependent short-lived increase in short-circuit current and a more prolonged equal effect on net Na and Cl fluxes. The latter consisted primarily of inhibition of mucosal-to-serosal fluxes of both Na and Cl. In addition serosal serotonin decreased ileal Na influx from the mucosal solution into the epithelium, suggesting an effect on Na absorption. Serotonin did not alter all aspects of ileal absorptive function and did not affect glucose-dependent Na absorption. Consistent with serotonin acting by inhibiting NaCl absorption in the ileum, serotonin induced equal inhibition of net Na and Cl absorption in rabbit gallbladder (which has a linked Na and Cl absorptive process) but had no effect on rabbit colon (which lacks a linked Na and Cl absorptive process). In addition, adenosine 3',5'-cyclic monophosphate and serotonin both appeared to alter the same ileal NaCl absorptive process, since following stimulation of ileal secretion with the maximum concentration of theophylline, addition of serotonin did not cause any further effects.

L-glutamine with D-glucose stimulates oxidative metabolism and NaCl absorption in piglet jejunum

1992 ◽  
Vol 263 (6) ◽  
pp. G960-G966 ◽  
Author(s):  
J. M. Rhoads ◽  
E. O. Keku ◽  
J. P. Woodard ◽  
S. I. Bangdiwala ◽  
J. G. Lecce ◽  
...  
Keyword(s):  
Oxidative Metabolism ◽  
Carbonic Acid ◽  
Apical Membrane ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Glutamine Metabolism ◽  
Nacl Absorption ◽  
The Relationship ◽  
Stimulation Of

To explore the relationship between intestinal fluid absorption and oxidative metabolism, we measured the effects of amino acids and glucose on piglet jejunal ion transport and oxygen consumption (QO2) in vitro. Jejunal QO2 was stimulated by L-glutamine and D-glucose but not by the nonmetabolizable organic solutes methyl beta-D-glucoside or L-phenylalanine. QO2 was maximally enhanced by the combination of D-glucose and L-glutamine (5 mM). Even though 5 mM L-glutamine was previously found to be insufficient to stimulate NaCl absorption, 5 mM L-glutamine enhanced jejunal NaCl flux when combined with equimolar mucosal D-glucose. Either D-glucose or methyl beta-D-glucoside caused an increase in short-circuit current (Isc), an increase in Na+ absorption in excess of Isc, and a decrease in Cl- secretion, when L-glutamine was substituted for D-glucose (10 mM) on the serosal side. This relationship suggests that mucosal sugars, if combined with L-glutamine, enhance neutral NaCl absorption as well as electrogenic Na+ flow. (Aminooxy)acetate, an inhibitor of alanine aminotransferase, abolished the stimulation of QO2 and the NaCl-absorptive response to L-glutamine. We conclude that the oxidative metabolism fueled by L-glutamine is linked to a NaCl-absorptive mechanism in the intestine. We propose that the CO2 produced by glutamine metabolism yields carbonic acid, which dissociates to H+ and HCO3-, which may stimulate parallel antiports in the apical membrane.

Suppression of coupled Na-Cl absorption by aldosterone and dexamethasone in rat distal colon in vitro

1984 ◽  
Vol 246 (6) ◽  
pp. F785-F793 ◽  
Author(s):  
R. D. Perrone ◽  
S. L. Jenks
Keyword(s):  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Rat Colon ◽  
Na Transport ◽  
Unidirectional Flux ◽  
Rat Distal Colon ◽  
Marked Suppression ◽  
Stimulation Of

Basal Na absorption in the rat colon is coupled to that of Cl in an electroneutral fashion. We previously determined that aldosterone or dexamethasone induces amiloride-sensitive mucosal-to-serosal Na flux approximately equal to the amiloride-sensitive short-circuit current in rat distal colon in vitro. However, the effect of these steroids on coupled Na-Cl absorption was not examined. For this purpose, we determined the unidirectional flux of Na and Cl in voltage-clamped distal colon segments from rats treated with aldosterone or dexamethasone. Amiloride was used as a probe for conductive Na absorption, and acetazolamide and Cl-free solutions were used as probes for coupled Na-Cl absorption. Our results indicate that the nature of colonic Na absorption is markedly changed after treatment with these steroids. In contrast to findings in the untreated rat, colonic Na absorption after treatment with aldosterone or dexamethasone was largely independent of the presence of Cl. Net Cl absorption and acetazolamide sensitivity were both greatly diminished. Thus, aldosterone and dexamethasone have multiple effects on Na transport in rat distal colon. In addition to the stimulation of conductive Na absorption by aldosterone, an effect well described in other epithelia, there is marked suppression of coupled Na-Cl absorption. Dexamethasone was less effective in suppressing Cl absorption but equally effective in stimulating conductive Na absorption. These steroid effects were greater in the terminal 1-2 cm of the rat colon.

Low-dose glucocorticoids maintain Na-H exchange in distal colon of adrenalectomized rats

1991 ◽  
Vol 261 (3) ◽  
pp. F545-F553 ◽  
Author(s):  
C. P. Bastl ◽  
L. Bressler ◽  
G. Schulman ◽  
M. Mendez ◽  
E. J. Cragoe
Keyword(s):  
Short Circuit ◽  
In Vitro Study ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ion Flux ◽  
Rat Colon ◽  
Anion Secretion ◽  
Stimulation Of

With in vivo perfusion we demonstrated that physiological doses of glucocorticoids restore Na and Cl absorption in adrenalectomized rat colon. The absorption is spironolactone and amiloride resistant and is inhibited by the Na-H inhibitor, 5-(N-ethyl-N-isopropyl)amiloride (EIPA), suggesting that glucocorticoids modulate Na-H antiport. The present in vitro study examines pathways mediated by glucocorticoids in adrenalectomized rat distal colon and rectum. In vivo administration of 2.5 micrograms/100 g body wt dexamethasone did not alter serosal-to-mucosal flux or tissue electrical parameters but restored mucosal-to-serosal flux and net Na and Cl absorption within 2–3 h of administration to levels found in intact rat colon. Transport was not inhibited by 10(-5) M amiloride but was eliminated by 10(-5) M EIPA. After 26 h of dexamethasone, an amiloride-resistant short-circuit current was stimulated, accompanied by increased residual ion flux in rectum, but not distal colon, suggesting that a delayed or secondary effect of glucocorticoids is stimulation of electrogenic anion secretion. Thus adrenalectomy reduces net ion flux in distal colon by its effect on electroneutral mucosal-to-serosal NaCl flux. Small doses of glucocorticoids completely ameliorate this effect via stimulation of the Na-H antiport. Glucocorticoids maintain basal electroneutral NaCl absorption in distal rat colon.

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