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Biomedical subjects

K A Hubel

Publications and source records attributed to K A Hubel.

At least 19 recordsLinked to original sources
PubMed1991

Secretory reflexes in ileum and jejunum: absence of remote effects.

We have tested the hypothesis that luminal secretagogues initiate neural reflexes that alter ion transport in small intestinal segments proximal or distal to the site of the secretory stimulus. Effects of secretagogues that act by different mechanisms were studied in vitro by measuring short circuit current (ISC) of ileum or jejunum mounted in a unique flux chamber while proximal mucosa in neural continuity with the tissue was perfused with secretagogues (Na deoxycholate. Escherichia coli STa, 5-hydroxytryptamine, theophylline) or was stimulated electrically (EFS). No proximal stimulus affected distal ISC. We also studied in vivo adjacent segments of ileum or jejunum in neural continuity but with unconnected lumens. In anesthetized rabbits, we measured transmural electrical potential difference and fluid movement (Phenol red marker). Stimulation of proximal segments of ileum or jejunum with STa, or of ileum with 5-HT or Na deoxycholate did not affect distal transport. Stimulation of distal segments of ileum and jejunum with STa or 5-HT, or of jejunum with Ha deoxycholate did not affect proximal transport. We conclude that the secretion caused by luminal secretagogues in the rabbit small intestine is limited to the area of stimulation.

Animals↗
PubMed1990

Ion transport in normal and inflamed human jejunum in vitro. Changes with electric field stimulation and theophylline.

We studied ion transport in human jejunal mucosa under basal conditions and when tissues were stimulated electrically (EFS) and with theophylline 5 mM (N = 12 pairs). Tissues were mounted in a flux chamber to measure unidirectional fluxes of 22Na, 36Cl, short-circuit current, Isc (mueq/cm2/hr), electrical potential difference, PD (mV), and total ionic conductance, G (mS/cm2). Six pairs of tissues that were normal or less inflamed responded to theophylline by increasing PD and Isc and by reducing JCl(ms), the mucosal to serosal flux of Cl. In six pairs that did not respond to theophylline or to EFS, inflammation was more intense, and in the basal state, G was lower, PD was higher, and unidirectional fluxes of Na and Cl were halved. We conclude: (1) normal jejunum secretes Cl and responds to theophylline or EFS by reducing JCl(ms) thereby increasing Cl secretion; (2) unlike human ileum, neither theophylline nor EFS affect JCl(sm); (3) inflammation eliminates the response to theophylline and to EFS.

Biological Transport↗
PubMed1989

Noradrenergic influence on epithelial responses of rabbit ileum to secretagogues.

Norepinephrine is one of three neurotransmitters that may act directly on enterocytes to enhance absorption; its interaction with secretagogues is of physiological importance. We have studied the influence of norepinephrine on the short-circuit current (Isc) responses to acetylcholine (ACh; 10 microM), vasoactive intestinal polypeptide (VIP; 100 pM-10 nM), peptide histidine isoleucine (PHI; 100 pM-10 nM), histamine (0.1 mM), and to electrical field stimulation (EFS) of rabbit ileum mounted in flux chambers. Tetrodotoxin reduced the response to norepinephrine (10 microM) by 40% and to histamine by 32% but did not affect responses to VIP or PHI. Norepinephrine decreased the ACh response (EC50, 70 nM) and reduced the responses to PHI (less than or equal to 87%), to EFS (less than or equal to 75%), and to histamine (less than or equal to 42%). Norepinephrine decreased the response to VIP (500 pM) but not to higher or lower VIP concentrations. It enhanced the response to VIP (10 nM) and to theophylline (5 mM). We conclude that 1) norepinephrine increases absorption by acting on nerves and enterocytes; 2) the failure of norepinephrine to reduce the Isc response to VIP when the VIP-induced increment in Isc is comparable to that caused by EFS is evidence that VIP does not mediate the EFS response; 3) PHI might mediate the EFS response; and 4) VIP, PHI, and histamine affect enterocytes directly; histamine also affects intrinsic nerves.

Acetylcholine↗
PubMed1988

The neurosecretory effect of ouabain on isolated rabbit ileal mucosa.

Ouabain, when added to fluid bathing rabbit ileal mucosa mounted in a flux chamber, transiently increases short circuit current, implying a paradoxical secretory response. To determine the cause of this change, we studied unidirectional fluxes of 36Cl and 23Na and the effects of ion substitution, of reduced Ca concentration, verapamil, tetrodotoxin and atropine. Ouabain 0.1 mM, transiently increased the serosal to mucosal flux of Cl and Na, increased Isc and PD and reduced ion conductance. The Isc response to ouabain was diminished by reducing the bath fluid concentration of Cl, of Ca, and by adding verapamil. Tetrodotoxin both delayed and reduced the maximal Isc response; atropine had no effect. We conclude that ouabain acts by releasing a neurotransmitter of unknown identity and by increasing the serosal to mucosal flux of Cl.

Animals↗
PubMed1987

Ion transport in human cecum, transverse colon, and sigmoid colon in vitro. Baseline and response to electrical stimulation of intrinsic nerves.

In a flux chamber study of ion transport in human colon, we compared baseline rates with those measured during electrical stimulation of intrinsic nerves. In baseline studies, sodium was absorbed throughout, but maximally in transverse colon. In cecum, sodium absorption accounted for the short circuit current and chloride was not absorbed. Chloride was absorbed in transverse and sigmoid colon, however. Residual current was minimal in cecum and transverse colon, but increased in sigmoid colon. Neural stimulation caused chloride secretion in cecum, reduced chloride absorption in sigmoid colon, but caused no change in transverse colon; sodium absorption decreased in cecum. A neurotransmitter of unknown identity affects baseline short circuit current in sigmoid colon. Half of the increase in short circuit caused by neural stimulation in sigmoid colon is mediated by muscarinic receptors. The identity of the other transmitter(s) is not known. It is not substance P or histamine. The three divisions of the colon differ in relative rates of baseline ion transport and in their transport responses to intrinsic nerve stimulation.

Cecum↗
PubMed1986

Effect of neuropeptide Y on ion transport by the rabbit ileum.

Neuropeptide Y (NPY) is present in fibers extending from the submucous plexus to the epithelium of the small intestine where the liberation of NPY might affect ion transport. We sought the effects of NPY on rabbit ileal mucosa stripped of muscularis propria and mounted in a flux chamber. NPY reduced the transmural electrical potential difference and short circuit current (Isc) and increased total ionic conductance. Threshold and maximal effects were evoked at concentrations of 1 nM and 1 microM, respectively. NPY increased chloride absorption, JCl(net), by increasing the flux of Cl from mucosa to serosa, JCl(ms), and by decreasing JCl(sm). JNa(net) actually diminished because JNa(sm) rose more than JNa(ms). In the presence of NPY theophylline 5 mM caused Cl secretion, increased potential difference and Isc and reduced total ionic conductance, indicating that the tissue could respond to a secretagogue. Tetrodotoxin 0.1 microM did not diminish the Isc reduction caused by NPY, and desensitization did not alter the response of the tissue to electrical field stimulation. Like somatostatin and norepinephrine, which are also present in the submucous plexus, NPY increases Cl absorption, but unlike them, it reduces rather than augments Na absorption. The lack of effect of tetrodotoxin on the Isc response to NPY implies that NPY does not act by liberating a second neurotransmitter; the lack of effect of NPY desensitization indicates that the liberation of NPY plays no significant role in the response of the tissue to electrical field stimulation.

Animals↗
PubMed1985

Intestinal nerves and ion transport: stimuli, reflexes, and responses.

The effects of extrinsic and intrinsic nerves on ion and water transport by the intestine are considered and discussed in terms of their possible physiological function. Adrenergic nerves enter the small intestine via mesenteric nerves. Adrenergic tone is usually absent in tissues in vitro but is present in vivo. The nerves increase absorption in response to homeostatic changes associated with acute depletion of extracellular fluid. Cholinergic tone that reduces fluid absorption or causes secretion has been detected in the small intestine of humans, dogs, and cats and in the colon of humans. Extrinsic cholinergic fibers generally do not affect ion transport in small intestine but probably do so in colon. Whether peptides liberated in the mucosa affect enterocytes directly is not clear. Studies on humans and rabbits suggest that the role of substance P is minor. The physiological roles of vasoactive intestinal polypeptide (VIP) and somatostatin remain to be defined. Intraluminal factors also affect ion and water transport. Mucosal rubbing, distension, and cholera toxin cause fluid secretion; acid solutions in the duodenum cause alkaline secretion; these stimuli and hypertonic glucose liberate serotonin into the lumen, the mesenteric venous blood, or both. It has been proposed that the enterochromaffin cell is an epithelial sensory cell that responds to noxious stimuli within the lumen by liberating serotonin. The serotonin initiates a neural reflex through a nicotinic ganglion to liberate a secretagogue that acts on the enterocyte. The function of VIP in this proposed reflex is unclear. The variety of intraluminal stimuli that influence epithelial function implies that there is more than one type of epithelial sensory cell (or sensory mechanism). Prostaglandins may mediate the alkaline secretion caused by acid in the duodenum. There may be other effective substances. Although it has been known for years that intraluminal stimuli affect the coordination of smooth muscle functions, it is not known whether similar stimuli also influence salt and water transport as a meal traverses the alimentary canal.

Amino Acids↗
PubMed1978

The effects of electrical field stimulation and tetrodotoxin on ion transport by the isolated rabbit ileum.

To determine whether intramural nerves affect intestinal ion transport, we studied the effect of electrical field stimulation (EFS) on the movement of ions across isolated rabbit ileum. EFS increased the transmural electrical potential difference and the short circuit current (Isc), caused C1 secretion, and reduced conductance, but did not alter fluxes of Na or the residual current (JRnet). The neurotoxin, tetrodotoxin, prevented all the changes caused by EFS but did not prevent the increase in Isc caused by theophylline (5 mM), carbachol (10 micrometer), or glucose (10 mM), or the reduction in Isc caused by norepinephrine (10 micrometer), implying that tetrodotoxin prevented responses to EFS by affecting electrically excitable cells rather than epithelial cells. Tetrodotoxin also enhanced the mucosa to serosa fluxes of Na and C1, reduced the potential difference and Isc, and increased conductance. The site of tetrodotoxin action is uncertain because it may affect the release of at least four neuro-transmitters and the release of peptides from endoctine cells. The Isc response to EFS was not affected by atropine (10 micrometer), physostigmine (10 micrometer), or by hemicholinium (1 micrometer). The mechanism by which EFS causes C1 secretion remains to be determined.

Animals↗
PubMed1976

Intestinal ion transport: effect of norepinephrine, pilocarpine, and atropine.

The effects of parenteral pilocarpine, atropine, and norepinephrine on salt and water transport were studied in jejunum and ileum of anesthetized rats. Pilocarpine increased jejunal transmural PD, reduced absorption of Na, K, HCO3, and H2O, and increased secretion of Cl; in ileum, it caused secretion of Na and H2O, elicited secretion of K, and reduced the absorption of Cl. In both segments, perfusate became more akaline, and there was less of a rise in PCO2. Atropine prevented all changes caused by pilocarpine. Atropine alone increased jejunal absorption of Na and HCO3 and acidity of perfusate, implying that cholinergic nerves influence transport. Norepinephrine augmented jejunal absorption of Na, Cl, and H2O but caused no change in PD. In ileum, norepinephrine increased absorption of Na and Cl, reduced the rise in pH, increased the rise in PCO2 of perfusate, but did not affect net HCO3 movement. With all agents, when Na absorption increased, perfusate became more acidic in jejunum and less alkaline in ileum, evidence of an association between Na and H transport.

Animals↗
PubMed1974

The mechanism of bicarbonate secretion in rabbit ileum exposed to choleragen.

BICARBONATE MAY BE SECRETED INTO THE INTESTINAL LUMEN IN CHOLERA BECAUSE: HCO(3) (-) ions are transported, or because OH(-) ions accumulate and react with dissolved CO(2) to form HCO(3) (-). If HCO(3) (-) ions are transported into the lumen from the interstitial fluid, lumenal P(CO2) should increase (HCO(3) (-) right harpoon over left harpoon OH(-) + CO(2)); if OH(-) accumulates, P(CO2) should diminish. Net movement of H(2)O, and HCO(3) (-), and changes in pH and P(CO2) in lumenal fluid were studied in adjacent segments of rabbit ileum in vivo, one of which was exposed to choleragen. 4 h after exposure, segments were drained and infused with gassed Krebs-Henseleit solution whose P(CO2) exceeded arterial P(CO2). After 45 min, fluid was collected anaerobically from control and cholera segments. Among 13 cholera segments, lumenal P(CO2) diminished by a mean of 8.4 torr and was less than femoral arterial blood in six instances. In the paired control segments, mean P(CO2) increased by 4.4 torr, and was always greater than arterial P(CO2). Dilution could not account for the low P(CO2) in cholera segments because in hypertonic solutions that caused water to move into the lumen, the P(CO2) did not differ from control values obtained with isotonic solutions. The results suggest that OH(-) accumulation (by addition of OH(-) or removal of H(+)) causes HCO(3) (-) secretion in cholera. This does not result from secretion of some other base (e.g., HPO(4) (-)), because HCO(3) (-) accounts for most of the base in the lumenal fluid. The P(CO2) changes suggest that OH(-) reacts with CO(2) at the cell-lumen interface, but reaction at the cell-interstitial fluid interface cannot be excluded.

Animals↗
PubMed1973

Effect of luminal sodium concentration on bicarbonate absorption in rat jejunum.

An exchange of Na(+) for H(+) has been proposed to explain why jejunal Na(+) absorption is influenced by luminal concentrations of H(+) and HCO(3) (-). We studied the influence of luminal Na(+) concentration on net HCO(3) (-) absorption by perfusing rat jejunum in vivo. When Na(+) was omitted from the perfusion fluid, HCO(3) (-) absorption diminished by a fixed amount over a range of initial HCO(3) (-) concentrations of 15 to 80 mM. This change was not caused by alterations in transmural PD or direction of water movement. Because the rate of HCO(3) (-) absorption decreased as the luminal HCO(3) (-) concentration lessened, Na(+)-dependent HCO(3) (-) absorption accounted for an increasing percent of total absorption as the luminal concentration of HCO(3) (-) diminished. The effect of Na(+) on HCO(3) (-) absorption is mediated, at least in part, by H(+) secretion, because luminal CO(2) production (manifested by luminal P(CO2)) dimished as HCO(3) (-) absorption decreased. The changes in P(CO2) are caused by reaction of H(+) with HCO(3) (-) in the luminal fluid because luminal P(CO2) is augmented by the presence of HCO(3) (-) and is diminished by addition of phosphate or Tris buffer. Whether all H(+) secretion requires luminal Na(+) cannot be determined with these experimental techniques because mucosal permeability to Na(+) and the unstirred layer make it impossible to eliminate Na(+) ions from the luminal cell surface. The nature of the mechanism for HCO(3) (-) transport that is not sodium dependent remains to be determined.

Bicarbonates↗