Inhibition of VIP-stimulated ion transport by a novel Y-receptor phenotype in rabbit distal colon

1993 ◽  
Vol 264 (5) ◽  
pp. G848-G854 ◽  
Author(s):  
G. H. Ballantyne ◽  
J. R. Goldenring ◽  
F. X. Fleming ◽  
S. Rush ◽  
J. S. Flint ◽  
...  
Keyword(s):  
Ion Transport ◽  
Colonic Mucosa ◽  
Peptide Yy ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ussing Chambers ◽  
Potent Inhibition ◽  
Colonic Secretion ◽  
Receptor Phenotype

Neurocrine, endocrine, and paracrine regulators are critical to the control of colonic secretion. These studies have investigated the inhibition of vasoactive intestinal polypeptide (VIP)-stimulated ion transport by peptide YY (PYY) and other Y-class effectors in rabbit distal colonic mucosa mounted in Ussing chambers. PYY decreased basal short-circuit current (Isc) but did not significantly change either basal Na+ or Cl- flux. PYY inhibited VIP-stimulated increases in Isc by up to 86% and abolished VIP-induced Cl- secretion. PYY decreased VIP-generated increases in Isc by a tetrodotoxin-insensitive mechanism. PYY inhibited cholera toxin-stimulated as well as forskolin-stimulated increases in Isc but failed to alter stimulation by 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP). PYY decreased VIP-stimulated increases in tissue cAMP by 88% and forskolin-stimulated increases by 84%. PYY, neuropeptide Y (NPY), (Leu31,Pro34)-NPY, and pancreatic polypeptide (PP) all demonstrated potent inhibition of VIP-stimulated increases in Isc. PYY-(13-36) demonstrated little effect on VIP stimulation. Thus the rabbit distal colon possesses a novel Y-class receptor phenotype that demonstrates high affinity for all three PP-fold peptides, NPY, PYY, and PP.

Neuromodulation of ion transport in porcine distal colon: NPY reduces secretory actions of leukotrienes

1995 ◽  
Vol 269 (2) ◽  
pp. R426-R431 ◽  
Author(s):  
T. R. Traynor ◽  
D. R. Brown ◽  
S. M. O'Grady
Keyword(s):  
Ion Transport ◽  
Colonic Mucosa ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Effective Concentration ◽  
Leukotriene C4 ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Half Maximal Effective Concentration

Electrical transmural stimulation (ETS) was used to examine the neuroregulation of electrolyte transport in the porcine distal colon. ETS of the colonic mucosa-submucosa mounted in Ussing chambers produced rapid and transient increases in short-circuit current (Isc) that were inhibited 36% by serosal bumetanide, suggesting that a portion of the response may be attributed to Cl secretion. ETS actions were dependent upon stimulus intensity and frequency and were inhibited by tetrodotoxin and omega-conotoxin. Prazosin and pyrilamine had no effect on the mucosal responses to ETS, whereas atropine reduced the responses by 32%. Neuropeptide Y (NPY) also reduced the mucosal responses to ETS up to 60% (half-maximal effective concentration = 17 nM). In addition, the effects of leukotriene C4, previously shown to stimulate Cl secretion via a neuronal pathway, were also inhibited by NPY. These results indicate that cholinergic submucosal neurons play a role in the regulation of epithelial ion transport and that NPY acts as an inhibitory neuromodulator, particularly on leukotriene-sensitive neurons in the porcine distal colon.

Taurodeoxycholate and the developing rabbit distal colon: absence of secretory effect

1987 ◽  
Vol 253 (4) ◽  
pp. G483-G488 ◽  
Author(s):  
G. D. Potter ◽  
R. Lester ◽  
S. M. Burlingame ◽  
P. A. Mitchell ◽  
K. L. Schmidt
Keyword(s):  
Ion Transport ◽  
Bile Acids ◽  
Phorbol Ester ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Fluid Secretion ◽  
Secretory Response ◽  
Ussing Chambers ◽  
Cl Secretion

Failure to absorb bile acids by the ileum leads to fluid secretion by the colon and diarrhea in adults. The infant ileum, however, does not actively transport bile acids. Therefore, we investigated the effect of taurodeoxycholic acid (TDCA) on ion transport in the colon of rabbits 7-10 days old. We mounted distal colon from infant and adult rabbits in modified Ussing chambers and exposed the mucosal or serosal surfaces to TDCA. In the adult, 50 microM TDCA produced an increase in short-circuit current (delta Isc = 1.0 +/- 0.3 mu eq . h-1 . cm-2, P less than 0.05) and Cl secretion. In the infant, the effect was different, Isc was reduced (delta Isc = -1.1 +/- 0.2 mu eq . h-1 . cm-2, P less than 0.01) and ion flux was not altered. Microscopy demonstrated that the infant epithelium was not significantly damaged by exposure to TDCA at these concentrations. The infant colon was, however, capable of a secretory response to a variety of agonists including theophylline, carbachol, bradykinin, serotonin, and 12,13-dibutyryl phorbol ester. The infant rabbit distal colon lacks a secretory response to TDCA during that period when the ileum cannot transport bile acids.

Stimulation of chloride secretion by baicalein in isolated rat distal colon

2002 ◽  
Vol 282 (3) ◽  
pp. G508-G518 ◽  
Author(s):  
W. H. Ko ◽  
V. W. Y. Law ◽  
W. C. Y. Yip ◽  
G. G. L. Yue ◽  
C. W. Lau ◽  
...  
Keyword(s):  
Colonic Mucosa ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Transmembrane Conductance Regulator ◽  
Transmembrane Conductance ◽  
Ussing Chambers ◽  
Rat Distal Colon ◽  
Cystic Fibrosis Transmembrane

The effect of baicalein on mucosal ion transport in the rat distal colon was investigated in Ussing chambers. Mucosal addition of baicalein (1–100 μM) elicited a concentration-dependent short-circuit current ( I sc) response. The increase in I sc was mainly due to Cl−secretion. The presence of mucosal indomethacin (10 μM) significantly reduced both the basal and subsequent baicalein-evoked I sc responses. The baicalein-induced I sc were inhibited by mucosal application of diphenylamine-2-carboxylic acid (100 μM) and glibenclamide (500 μM) and basolateral application of chromanol 293B (30 μM), a blocker of KvLQT1 channels and Ba2+ ions (5 mM). Treatment of the colonic mucosa with baicalein elicited a threefold increase in cAMP production. Pretreating the colonic mucosa with carbachol (100 μM, serosal) but not thapsigargin (1 μM, both sides) abolished the baicalein-induced I sc. Addition of baicalein subsequent to forskolin induced a further increase in I sc. These results indicate that the baicalein evoked Cl− secretion across rat colonic mucosa, possibly via a cAMP-dependent pathway. However, the action of baicalein cannot be solely explained by its cAMP-elevating effect. Baicalein may stimulate Cl− secretion via a cAMP-independent pathway or have a direct effect on cystic fibrosis transmembrane conductance regulator.

Regional differences in the response to platelet-activating factor in rabbit colon

1992 ◽  
Vol 82 (6) ◽  
pp. 673-680 ◽  
Author(s):  
S. P. L. Travis ◽  
D. P. Jewell
Keyword(s):  
Ion Transport ◽  
Regional Differences ◽  
Chloride Transport ◽  
Short Circuit ◽  
Platelet Activating Factor ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Chloride Secretion ◽  
Anion Secretion ◽  
Ussing Chambers

1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers. 2. The effect of platelet-activating factor (1–50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA. 3. Colonic permeability, assessed by transmucosal resistance and mannitol flux, was increased by platelet-activating factor in both the distal colon and the caecum. This was consistent with an effect on platelet-activating factor on the paracellular pathway, because resistance decreased even when transcellular chloride transport was inhibited by frusemide or ion replacement. A specific platelet-activating factor antagonist (U66985) inhibited the effects of platelet-activating factor in both the distal colon and the caecum. 4. The results show that platelet-activating factor stimulates anion secretion only in the distal colon, but increases permeability in both the caecum and the distal colon.

Regulation of colonic ion transport by GRP. I. GRP stimulates transepithelial K and Na secretion

1996 ◽  
Vol 270 (3) ◽  
pp. C848-C858 ◽  
Author(s):  
T. R. Traynor ◽  
S. M. O'Grady
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Basolateral Membrane ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Transient Increase ◽  
Transport Pathway ◽  
Ussing Chambers ◽  
Intracellular Ca ◽  
Distal Colon Epithelium

Regulation of electrolyte transport across porcine distal colon epithelium by gastrin-releasing peptide (GRP) was examined using mucosal sheets mounted in Ussing chambers. Serosal GRP produced a biphasic response consisting of a transient increase in short-circuit current (ISC) followed by a long-lasting decrease. Indomethacin and tetrodotoxin inhibited the ISC increase without affecting the secondary decrease. Addition of GRP to the mucosal solution produced a decrease in ISC similar to that observed with serosal treatment, but no transient increase in ISC was observed. GRP and bombesin (50% effective concentrations of 26 and 30 nM, respectively) were more effective than neuromedin B in decreasing the ISC, and the GRP receptor antagonist [D-Phe(6)]bombesin(6-13)-O-methyl produced a sixfold dextral shift in the GRP concentration-response relationship. The GRP-stimulated decrease was reduced in the absence of Cl and by serosal bumetanide. Flux measurements showed that GRP increased Rb and Na secretion while having no effect on transepithelial Cl transport. Phosphoinositide turnover was increased by GRP, suggesting that the ion transport changes may be mediated by intracellular Ca concentration. The results of this study demonstrate that GRP stimulates K and Na secretion across the porcine distal colon epithelium and that these processes are dependent, in part, on a bumetanide-sensitive transport pathway located in the basolateral membrane.

Histamine augments colonic secretion in guinea pig distal colon

1990 ◽  
Vol 258 (3) ◽  
pp. G432-G439 ◽  
Author(s):  
Y. Z. Wang ◽  
H. J. Cooke ◽  
H. C. Su ◽  
R. Fertel
Keyword(s):  
Short Circuit ◽  
Nordihydroguaiaretic Acid ◽  
Short Circuit Current ◽  
Intestinal Secretion ◽  
Distal Colon ◽  
H2 Antagonist ◽  
Colonic Secretion ◽  
Set Up ◽  
Colonic Transport

We tested the hypothesis that the role of histamine in the control of intestinal secretion is mediated by prostaglandins (PGs). The effects of histamine on ion transport were examined in muscle-stripped sheets of mucosa/submucosa set up in flux chambers. Histamine evoked a transient concentration-dependent increase in short-circuit current (Isc) that was reduced by the Cl- transport inhibitor bumetanide. Histamine also caused the release of PGE2. The Isc response to histamine was reduced by indomethacin and piroxicam, which block PG formation, but not by nordihydroguaiaretic acid, which prevents production of lipoxygenase products. 2-Methylhistamine, but not dimaprit, evoked a concentration-dependent increase in Isc. The Isc response to histamine was reduced by the H1-blocker pyrilamine, but not by the H2-antagonist cimetidine. In addition to its direct effect, histamine augmented the responses of endogenously released neurotransmitters with and without indomethacin and hexamethonium. Tetrodotoxin (TTX) reduced the Isc response to 10(-3) M histamine. In the presence of TTX, exogenous histamine amplified the responses to PGs, vasoactive intestinal polypeptide, 2-chloroadenosine, bethanechol, and carbachol. These results suggest that histamine acts at H1-receptors on cells within the gut to mediate intestinal Cl- secretion in part by releasing PGs and by augmenting the actions of endogenously released neurotransmitters. Our results indicate that histamine has a role in the regulation of colonic transport function.

Corticosteroid alteration of active electrolyte transport in rat distal colon

1983 ◽  
Vol 245 (5) ◽  
pp. G668-G675 ◽  
Author(s):  
E. S. Foster ◽  
T. W. Zimmerman ◽  
J. P. Hayslett ◽  
H. J. Binder
Keyword(s):  
Colonic Mucosa ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Transport Processes ◽  
Electrolyte Transport ◽  
Sodium Absorption ◽  
Rat Distal Colon ◽  
Potassium Absorption ◽  
Potassium Secretion

To determine the effect of corticosteroids on active transport processes, unidirectional fluxes of 22Na, 36Cl, and 42K were measured under short-circuit conditions across isolated stripped distal colonic mucosa of the rat in control, secondary hyperaldosterone, and dexamethasone-treated animals. In controls net sodium and chloride fluxes (JNanet and JClnet) and short-circuit current (Isc) were 6.6 +/- 2.2, 7.6 +/- 1.6, and 1.3 +/- 0.2 mu eq X h-1 X cm-2, respectively. Although aldosterone increased Isc to 7.3 +/- 0.5 mu eq X h-1 X cm-2, JNanet (6.9 +/- 0.7 mu eq X h-1 X cm-2) was not altered and JClnet was reduced to 0 compared with controls. Dexamethasone also stimulated Isc but did not inhibit JClnet. In Cl-free Ringer both aldosterone and dexamethasone produced significant and equal increases in JNanet and Isc. Theophylline abolished JNanet in control animals but not in the aldosterone group. Aldosterone reversed net potassium absorption (0.58 +/- 0.11 mu eq X h-1 X cm-2) to net potassium secretion (-0.94 +/- 0.08 mu eq X h-1 X cm-2). Dexamethasone reduced net potassium movement to 0 (-0.04 +/- 0.12 mu eq X h-1 X cm-2). These studies demonstrate that 1) corticosteroids stimulate electrogenic sodium absorption and 2) aldosterone, but not dexamethasone, inhibits neutral NaCl absorption and stimulates active potassium secretion. The effects of mineralocorticoids and glucocorticoids on electrolyte transport are not identical and may be mediated by separate and distinct mechanisms.

Ion transport across cat and ferret tracheal epithelia

1986 ◽  
Vol 61 (3) ◽  
pp. 1065-1070 ◽  
Author(s):  
R. J. Corrales ◽  
D. L. Coleman ◽  
D. B. Jacoby ◽  
G. D. Leikauf ◽  
H. L. Hahn ◽  
...  
Keyword(s):  
Ion Transport ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Free Medium ◽  
Mucin Secretion ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
Mucosal Side

Sheets of trachea from ferret and cat were mounted in Ussing chambers and continuously short circuited. Under resting conditions, in both the cat and ferret there was little or no Cl secretion, and Na absorption accounted for most of the short-circuit current (Isc). Ouabain (10(-4) M, serosal bath) reduced Isc to zero in 30–60 min. This decline was matched by a decrease in net Na absorption. Amiloride (10(-4) M, luminal bath) caused a significant decrease in Isc and conductance (G) in both species. Bumetanide (10(-4) M, serosal bath) had negligible effects on Isc and G. In both species, isoproterenol increased Isc by stimulating Cl secretion. Methacholine induced equal amounts of Na and Cl secretion, with little change in Isc. In the cat, prostaglandins E2 and F2 alpha and bradykinin increased Isc, responses which were abolished in Cl-free medium. In open-circuited cat tissues, Na flux from the serosal to mucosal side was measured simultaneously with the secretion of nondialyzable 35S. Prostaglandins E1, E2, and F2 alpha, histamine, bradykinin, methacholine and isoproterenol all increased both Na and 35S-mucin secretion.

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.

Brain natriuretic peptide stimulates K and Cl secretion across porcine distal colon epithelium

1991 ◽  
Vol 260 (4) ◽  
pp. C750-C755 ◽  
Author(s):  
T. R. Traynor ◽  
S. M. O'Grady
Keyword(s):  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Distal Colon ◽  
Ringer Solution ◽  
Ussing Chambers ◽  
Cl Secretion ◽  
The Difference ◽  
Distal Colon Epithelium

Porcine distal colon epithelium was mounted in Ussing chambers and bathed with porcine Ringer solution. The serosal addition of brain natriuretic peptide (BNP; 50 nM) or atriopeptin III (AP-III; 500 nM) produced significant increases (50-75 microA/cm2) in short-circuit current (Isc). These increases in Isc were not inhibited by pretreatment with tetrodotoxin (TTX) or 5,8,11,14-eicosatetraynoic acid (ETYA). Analysis of concentration-response relationships revealed that BNP was 5.8-fold more potent than AP-III in stimulating the Isc. BNP and AP-III significantly increased the serosal-to-mucosal (S----M) Cl flux and reduced net Cl absorption by 38 and 41%, respectively. The BNP-stimulated S----M Cl flux was abolished when HCO3 was removed. In contrast, the vasoactive intestinal peptide (VIP)-stimulated S----M Cl flux was not affected by HCO3 replacement. In addition to their effects on Cl transport, BNP and AP-III increased net Rb secretion by 79 and 58%, respectively. BNP-stimulated Rb secretion was reduced by 76% after HCO3 replacement. These results indicate that natriuretic peptides stimulate K- and HCO3-dependent Cl secretion which is not present under basal conditions or after VIP stimulation. The difference in potency between BNP and AP-III suggests that ANP-B receptors may mediate their effects on ion transport in the porcine colon.

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