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At least 19 recordsLinked to original sources

Histologic changes in neuronal innervation of the ileum mucosa after autologic-allotopic ileum mucosa transplantation.

INTRODUCTION: After successful experimental autologic-allotopic ileum mucosa transplantation, we investigated the remodeling of the transplanted submucous and mucous plexus, which is essential for the motility of the created colon coat-ileum mucosa complex. METHOD: In 8 beagles we transplanted ileum mucosa in a demucosed vascularized transverse colon segment, which was reanastomosed with the small bowel immediately after transplantation. Four weeks later the animals were sacrificed and histology specimens taken from the anastomosis site of the colon coat-ileum mucosa complex, allowed comparison between transplanted and normal mucosa in the same section. After fixation in 4% formaldehyde and PBS the samples were embedded in paraffin and 7 micro m sections were prepared. The distribution of nerve fibers and submucous ganglia were examined in dewaxed sections, using antisera against protein gene product (PGP9.5), a general neuronal marker. RESULTS: The submucosal ganglia were prominent in all samples but they were smaller and the submucous nerve cells within the ganglia were less numerous compared to the controls. The innervation of the transplanted ileum mucosa was reduced as the number of nerve fibers in the mucosal villi was decreased. Besides these neuromorphologic changes the transplanted mucosa showed a slightly higher rate of shortened villi compared to normal ileum mucosa. CONCLUSIONS: After ileum mucosa transplantation the submucosal ganglia are smaller and less numerous. Furthermore there is a considerable loss of nerve fibers in the mucosal layer. Additionally a loss of microvilli in the transplanted ileum mucosa was found. Whether these findings represent a state of remodeling or a slow atrophy of the enteric nervous system in the transplanted areas is currently under investigation.

Animals↗

The rat distal ileum has a reduced absorptive and secretory capacity compared with proximal ileum--is it to facilitate its chemosensing function?

Compared with the proximal ileum, the distal ileum in rat has a greatly reduced capacity for electrogenic ion secretion induced by secretagogues and for electrogenic, sodium-linked glucose transfer assessed in vitro. Similarly, in vivo, there is a great reduction in distal ileal basal fluid absorption and secretagogue-activated fluid secretion compared with proximal ileal values. This reduced absorptive and secretory capacity of the distal ileum would allow minimal changes in the concentrations of the luminal contents, facilitating its putative role as final chemosensor of the luminal contents of the small intestine.

Acetylcholine↗

[Pathophysiological study of the ileum after total colectomy in combination with mucosal proctectomy and ileoanostomy--the alteration in water and electrolyte absorption by the ileum after ileoanostomy].

We have developed a new procedure, total colectomy in combination with mucosal proctectomy and ileoanostomy, to preserve anorectal function for the patients with adenomatosis coli and ulcerative colitis. Using dialysis method, we evaluated the alteration of the ability to absorb water and electrolytes at the ileum after ileoanostomy in 12 patients with adenomatosis coli and 4 patients with ulcerative colitis, and compared the result with fecal volume and content to investigate compensatory function of the small intestine after total colectomy. Volume of water absorbed at the ileum was 0.389 g in an average soon after the first stage operation but gradually increased after the intestinal continuity was restored following the second stage operation with the volume of 0.666 g after 1 year and 0.702 g after 2 years (1.8 fold increase). Fecal volume excreted was 852 g/day in an average after loop ileostomy (first stage operation) but decreased to 316 g/day in a year after the second stage operation with simultaneous change of fecal character from watery to solid. The decrease of fecal volume was inversely correlated with the increase of the volume of water absorbed at the ileum (p less than 0.001). The ability to absorb electrolytes increased after the second stage operation compared to that of after the first stage operation but subsequently minimal change was noted. And the absorption pattern was different from that of the large intestine.

Adolescent↗

Disturbance of the prejunctional modulation of cholinergic neurotransmission during chronic granulomatous inflammation of the mouse ileum.

The effect of chronic granulomatous inflammation of the intestine was studied on the prejunctional modulation of cholinergic nerve activity in the mouse ileum. Contractions to carbachol (0.01 - 0.3 microM) and to electrical field stimulation (EFS, 0.25 - 8 Hz) of enteric neurons were higher in inflamed ileum as compared to control ileum. However, when the neurally-mediated contractions to EFS were expressed as percentage of the direct smooth muscle contraction to carbachol, the responses to EFS were similar in control and inflamed ileum. Atropine (1 microM) abolished all contractions to EFS and carbachol in control and inflamed ileum. DMPP (3 - 30 microM), a nicotinic receptor agonist, induced concentration-dependent contractions that were more pronounced in inflamed ileum as compared to control ileum. Hexamethonium (100 microM), a nicotinic receptor blocker, significantly inhibited the contractions to EFS in inflamed ileum but not in control ileum. In control ileum, histamine (10 - 100 microM) and the histamine H(1) receptor agonist HTMT (3 - 10 microM) inhibited the contractions to EFS concentration-dependently without affecting the contractions to carbachol. The inhibitory effect of histamine and HTMT was prevented by the histamine H(1) antagonist mepyramine (5 - 10 microM) but not by the H(2)- and H(3)-receptor antagonists cimetidine and thioperamide (both 10 microM). In chronically inflamed ileum however, histamine (10 - 100 microM) and HTMT (3 - 10 microM) failed to inhibit the contractions to EFS. The histamine H(2) and H(3) receptor agonists dimaprit and R(-)-alpha-methylhistamine did not affect the contractions to EFS in control and inflamed ileum. The alpha(2)-receptor agonist UK 14.304 (0.01 - 0.1 microM) inhibited the contractions to EFS in control and inflamed ileum without affecting the contractions to carbachol. The effect of UK 14.304 was reversed by the alpha(2)-receptor antagonist yohimbine (1 microM). The inhibitory effect of UK 14.304 on contractions to EFS was of similar potency in control and inflamed ileum. Our results suggest that the prejunctional modulation of cholinergic nerve activity by nicotinic and histaminic H(1) receptors is disturbed during chronic intestinal inflammation whereas the modulation by alpha(2)-receptors is preserved. Such a disturbance of cholinergic nerve activity may contribute to the motility disturbances that are often observed during chronic intestinal diseases in humans.

Adrenergic Agonists↗

Poor effect of glutamin and human-EGF on autologic-allotopic transplanted ileum mucosa.

INTRODUCTION: After establishing a new method of autologic-allotopic ileum mucosa transplantation as a therapy for short-bowel syndrome, the effects of glutamine and human epithelial growth factor (human EGF) on the transplanted ileum mucosa were evaluated. METHODS: Ileum mucosa was transplanted in 28 young beagle dogs in a demucosed vascularised transverse colon segment. The ileum mucosa was kept in place with silicone stents in all animals. Eight animals of the control group were irrigated with saline solution. In the second group with 10 animals, 100 mg/kg glutamine were administered daily in the lumen. The 10 animals of the third group were treated with 25 microg/kg human EGF per day subcutaneously and irrigated with saline solution. 4 weeks later, histological specimens were harvested from the colon coat-ileum mucosa complex, the normal ileum and normal colon. Lumen diameter, percentage ileum mucosa uptake as well as mucosa and colon muscle coat thickness were evaluated. RESULTS: In all groups, the diameter of the lumen was larger than 10 mm after fixation, due to the silicone stent. The group with glutamine irrigation showed the largest lumen diameter. A complete mucosa lining of the inner surface of the colon muscle coat was achieved in none of the animals. The highest percentage of ileum mucosa uptake was found in the group with glutamine irrigation. In most animals, the transplanted ileum mucosa was markedly thinner than normal ileum mucosa. Only in the group with glutamine irrigation did we find two animals with nearly normal mucosa thickness. The longitudinal muscle of the transplanted colon coat was thicker in all three groups compared to normal colon. There were no differences in thickness of the circular muscle in all animals compared to normal colon. CONCLUSIONS: Silicone stents maintain a lumen after autologic-allotopic ileum mucosa transplantation. However, additional irrigation with glutamine, as well as treatment with human EGF subcutaneously could not provide a complete lining of the colon muscle coat with transplanted ileum mucosa. A modification of the operative procedure is necessary to achieve a colon muscle coat that is completely lined with ileum mucosa before the absorptive capacity of the transplanted colon coat-ileum mucosa complex can be evaluated.

Animals↗

Pharmacological characterization of adrenoceptors mediating contractile and relaxant responses to noradrenaline in the longitudinal muscle of guinea-pig ileum.

Mechanical responses to noradrenaline (NA) were recorded in longitudinal muscle strips from the terminal and intermediate regions (3-10 cm and 30-40 cm from the ileo-caecal junction, respectively) of the guinea-pig ileum. NA(0.16-1,600 microM) produced a concentration-dependent contraction in the terminal ileum with the EC50 value of 11.9 +/- 4.3 microM (n = 5). In the intermediate ileum, NA produced relaxation at concentrations ranging from 0.016 microM to 1.6 microM. Responses to NA at 16 microM varied among preparations: no noticeable change in tension, a moderate relaxation and a small contraction. At higher concentrations, NA produced contractile responses and their peak tension increased in a concentration-dependent manner. The contractile effect of NA in the terminal ileum remained unaltered after treatment with propranolol (1.4 microM) or yohimbine (1.1 microM), or a combination of these drugs. In the intermediate ileum, the relaxant effect of NA was markedly reduced or abolished by propranolol (1.4 microM). Yohimbine (1.1 microM) had little effect on NA-induced relaxation. The contractile effect of NA in both the terminal ileum and intermediate ileum was inhibited by prazosin (1.1 microM), so that the contractions were converted to relaxation or markedly reduced. Propranolol abolished the relaxant response induced by NA at 0.16 microM, but did not inhibit those induced by NA at 1.6 microM. Methoxamine (0.16-1,600 microM) produced a concentration-dependent contraction in both the terminal ileum and the intermediate ileum. The EC50 was 93.5 +/- 28.5 microM (n = 8) in the terminal ileum and 83.3 +/- 27.7 microM (n = 10) in the intermediate ileum. There was no significant difference between the values. The results showed that NA is capable of producing contraction or relaxation in the longitudinal muscle layer of the terminal and intermediate regions of the guinea-pig ileum. The contraction, which is mediated by alpha 1-adrenoceptors, predominates in the terminal ileum, but relaxation, which is mediated by beta-adrenoceptors and uncharacterized adrenoceptors, predominates in the intermediate ileum.

Animals↗

Comparison of tachykinin NK1 and NK2 receptors in the circular muscle of the guinea-pig ileum and proximal colon.

1. The aim of this study was the pharmacological characterization of tachykinin NK1 and NK2 receptors mediating contraction in the circular muscle of the guinea-pig ileum and proximal colon. The action of substance P (SP), neurokinin A (NKA) and of the synthetic agonists [Sar9]SP sulphone, [Glp6,Pro9]SP(6-11) (septide) and [beta Ala8]NKA(4-10) was investigated. The affinities of various peptide and nonpeptide antagonists for the NK1 and NK2 receptor was estimated by use of receptor selective agonists. 2. The natural agonists, SP and NKA, produced concentration-dependent contraction in both preparations. EC50 values were 100 pM and 5 nM for SP, 1.2 nM and 19 nM for NKA in the ileum and colon, respectively. The action of SP and NKA was not significantly modified by peptidase inhibitors (bestatin, captopril and thiorphan, 1 microM each). 3. Synthetic NK1 and NK2 receptor agonists produced concentration-dependent contraction of the circular muscle of the ileum and proximal colon. EC50 values were 83 pM, 36 pM and 10 nM in the ileum, 8 nM, 0.7 nM and 12 nM in the colon for [Sar9]SP sulphone, septide and [beta Ala8]NKA-(4-10), respectively. The pseudopeptide derivative of NKA(4-10), MDL 28,564 behaved as a full or near-to-full agonist in both preparations, its EC50s being 474 nM and 55 nM in the ileum and colon, respectively. 4. Nifedipine (1 microM) abolished the response to septide and [Sar9]SP sulphone in the ileum and produced a rightward shift and large depression of the response in the colon. The response to [beta Ala8]NKA(4-10) was abolished in the ileum and largely unaffected in the colon. 5. The NK1 receptor antagonists, (+/-)-CP 96,34, FK 888 and GR 82,334 competitively antagonized the response to septide and [Sar9]SP sulphone in both preparations without affecting that to [beta Ala8]NKA(4-10). In general, the NK1 receptor antagonists were significantly more potent toward septide than [Sar9]SP sulphone in both preparations. 6. The NK2 receptor antagonists, GR 94,800 and SR 48,968 selectively antagonized the response to [beta Ala8]NKA(4-10) without affecting that to [Sar9]SP sulphone or septide in the ileum and colon. SR 48,968 produced noncompetitive antagonism of the response to the NK2 receptor agonist in the ileum and competitive antagonism in the colon. 7. MEN 10,376 and the cyclic pseudopeptide MEN 10,573 antagonized in a competitive manner the response to [beta Ala8]NKA(4-10) in the ileum and colon. While MEN 10,573 was equipotent in both preparations, MEN 10,376 was significantly more potent in the colon than in the ileum. MEN 10,376was also effective against septide in both preparations, without affecting the response to [Sar9] SP sulphone. MEN 10,573 antagonized the response to [Sar9]SP sulphone and septide in both preparations,pKB values against septide being intermediate, and significantly different from, those measured against[Beta Ala 8]NKA(4-10) and [Sa9]lSP sulphone.8. These findings show that tachykinin NK1 and NK2 receptors mediate contraction of the circular muscle of the guinea-pig ileum and colon. In both preparations NK1 receptor antagonists display higher apparent affinity when tested against septide than [Sar9]SP sulphone. These findings are compatible with the proposed existence of NK1 receptor subtypes in guinea-pig, although alternative explanations (e.g.agonist binding to different epitopes of the same receptor protein) cannot be excluded at present.Furthermore, an intraspecies heterogeneity of the NK2 receptor in the circular muscle of the guinea-pig ileum and colon is suggested.

Animals↗

Autologous-allotopic ileum mucosa transplantation for small bowel elongation. A morphological study.

INTRODUCTION: Since a standard therapy for short bowel syndrome does not yet exist, every search for new surgical methods would be worthwhile. In previous studies we could show that autologous-allotopic ileum mucosa transplantation is feasible. After a modification of our technique a vascularized colon muscle coat lined completely with transplanted ileum mucosa could be engendered. METHOD: In 12 young beagles autologous ileum mucosa was transplanted in a demucosed vascularized transverse colon segment. The colon coat-ileum mucosa complex was anastomosed with the small bowel immediately after transplantation, 4 weeks later the animals were sacrificed and histology specimens were harvested from the colon coat-ileum mucosa complex, normal ileum and normal colon. After fixation in 2.5% glutaraldehyde the samples were frozen (-40 degrees C) and 14 micro m sections were stained with hemalaun and eosin. The lumen diameter, the mucosa, submucosa and colon muscle coat thickness, as well as the mucosal crypt depth were evaluated. RESULTS: The diameter of the colon coat-ileum mucosa-complex was smaller than the diameter of normal ileum and colon with no significant stenosis. There were no marked differences in thickness of mucosa and depth of the mucosal crypts compared to the controls, but the transplanted mucosa showed a slightly higher rate of shortened villi. The submucosal layer was thicker following transplantation and showed good neovascularization. The circular muscle layer of the transplanted colon coat was up to 178% thicker and the thickness of the transplanted longitudinal muscle layer differed between 58% and 143% in comparison to normal colon. CONCLUSIONS: Only a few histologic differences between transplanted and normal ileum mucosa could be observed after autologous-allotopic ileum mucosa transplantation. Therefore a nearly normal function of the colon coat-ileum mucosa complex has to be expected. Long term experiments of the histologic changes as well as further functional studies are on-going in order to finally apply autologous-allotopic ileum mucosa transplantation clinically.

Animals↗

[Bacterial clearance of the terminal ileum in relation to the ileocolic connection].

The ecology of the (neo-)terminal ileum was investigated in three groups of mongrel dogs (group 1 to 3; 6 animals per each group) depending on the ileocolic connection and the resection of the terminal ileum. The efficacy of a stabilized nipple-valve-anastomosis (SNVA) was evaluated comparing the physiological ileocecal valve and the conventional end-end-anastomosis. The relations of the aerobic and anaerobic bacterial counts of all 18 dogs (group 0) preoperatively served as reference-values. Under this physiological condition the median counts were found to be lower in the ileum than in the colon, two logs for the aerobic bacteria and three logs for the anaerobic bacteria, confirming statistical significance (p < or = 0.05). The resection of the terminal ileum conserving the ileocecal valve (group 1) had no influence on the bacterial flora of the neoterminal ileum, whereas the limited resection of the ileocecal valve with ileocolic end-end-anastomosis (group 2) induced a bacterial colonisation of the terminal ileum. In contrast, following wide ileocoecal resection and replacement of the ileocecal valve by the SNVA (group 3) the bacterial counts were lower in the terminal ileum than in the colon: five logs for aerobic and seven logs for anaerobic bacteria. This difference was statistically significant within this group between ileum and colon and between ileum preoperatively and postoperatively (p < or = 0.05). In conclusion, the bacterial clearance of the (neo-)terminal ileum depends more on the retrograde barrier-function of the ileocecal valve or an appropriate mechanical substitute than on the propulsive motility of the ileum.(ABSTRACT TRUNCATED AT 250 WORDS)

Anastomosis, Surgical↗

Detubularization-induced contractile response change of the ileum following ileocystoplasty.

We reported previously that following ileocystoplasty the structure and pharmacologic response of the implanted ileum changes towards that of the bladder. Specifically, the relaxation response to alpha adrenergic (methoxamine) and purinergic (ATP) stimulation reverses to a contractile response one month after the ileal segment is surgically made part of the urinary bladder. The present study was designed to investigate possible signals for this change and also to determine whether bladder responses would mimic the ileum if surgically interposed into the ileal stream. Rabbits in group 1 underwent bladder interposition into the functioning terminal ileum, rabbits in group 2 underwent tubularized ileocystoplasty and rabbits in group 3 underwent detubularized ileocystoplasty with urinary diversion. Twelve rabbits survived and were available for evaluation; five in group 1, three in group 2 and four in group 3. Analysis was done six weeks after surgery. In group 1 animals, the interposed bladder showed epithelial changes towards ileum and also a change in its in-vitro contractile responses towards that of ileum. In group 2 animals the tubular cystoplastic ileum showed minimal functional and morphologic changes. In group 3 animals, the defunctionalized, detubular cystoplastic ileum showed alpha adrenergic and purinergic response changes towards bladder. These results indicate that detubularization with interruption in the arrangement of smooth muscle fibers as well as the breach in the integrity of neuronal connections is likely to be the primary signal for the change in the ileum towards bladder induced by cystoplasty. The results can not rule out reinnervation of the intestinal segment by bladder nerves. In addition these data demonstrate that the pharmacologic response of the bladder changes towards the ileum within six weeks after the bladder is surgically made part of the ileum.

Adenosine Triphosphate↗

Kindling-like convulsive activities in the isolated ileum of the guinea pig. I. Electrical stimulation.

A kindling-like convulsive activity model produced by subthreshold, iterative electrical stimulation of the isolated male guinea pig ileum is described. In this model, the mechanical activity of the longitudinal muscular fibers of the ileum was systematically quantified in terms of the basic frequency, tonus, amplitude, and transient amplitude increments (A, n spikes/20 min) of "normal" contractions and presence of high-amplitude, paroxysmal, "epileptiform" contractures (B, n spikes/20 min). Changes in these parameters were statistically compared through consecutive stages of the same stimulated male ileum (I = initial activation, II = initial inhibition. IIIA = late activation, and IV = late inhibition) and equivalent stages of stimulated female and nonstimulated male ilea where "kindling-like" activities were only occasionally observed. Basic tonus, amplitude, and number of A spikes showed significant changes through consecutive stimulated male ileum "kindling" stages: increased from baseline to stage I, decreased from I to II, increased from II to III and from III to IIIA, and decreased from IIIA to IV. The number of B spikes significantly increased from II to III, III to IIIA, and IIIA to IV. No significant changes in baseline frequency were found through all stages nor in tonus, amplitude, A and B spikes between stage IV and the self-sustained activity observed 120 min after stimulation. In addition, there were significant correlations between B spikes vs. basic tonus and amplitude and A spikes when the stimulated male ileum shifted from stage II to IIIA (positive correlations) and from IIIA to IV (negative correlations). Basic tonus during stage I, basic amplitude during IIIA, A spikes during self-sustained activity and B spikes during III, IIIA, IV, and self-sustained activity were in the stimulated male ileum larger than those in both the stimulated female and the nonstimulated male ilea. Tonus and A spikes during III and IIIA in the stimulated male ileum were larger than in the nonstimulated, whereas tonus during IV and self-sustaining activity and amplitude during II in the stimulated male ileum were smaller than in the female stimulated ileum.

Animals↗

Comparison of gamma-aminobutyric acid effects in different parts of the cat ileum.

The effects of gamma-aminobutyric acid (GABA) and those of a GABA(A) (muscimol) and a GABA(B) (baclofen) receptor agonists were determined on the spontaneous activity of longitudinally or circularly oriented preparations (segments) isolated from terminal, proximal and distal parts of the cat ileum. GABA applied at 1 microM to 2 mM caused dose-dependent biphasic changes (relaxation and contraction) in spontaneous activity of the longitudinal and circular layers in the terminal and distal parts of the cat ileum and monophasic changes (contraction) in the proximal part. The potency of GABA to elicit relaxant and/or contractile effects in different parts of the ileum showed a proximal-to-terminal increasing pattern. In the longitudinal layer of the distal and terminal ileum, muscimol (100 microM) mimicked the relaxation phase of the GABA effect, while baclofen (100 microM) simulated the contractile phase. Bicuculline, atropine and tetrodotoxin abolished GABA- and muscimol-induced relaxation and suppressed, but failed to prevent GABA- and baclofen-induced contractions. In addition, 2-hydroxysaclofen antagonized the baclofen-induced contractile effect, reduced the GABA-induced contractile phase but failed to prevent GABA- and muscimol-induced relaxation. In the circular layer of the same regions, muscimol mimicked the biphasic GABA effects, while baclofen was without effect. Bicuculline, atropine and tetrodotoxin completely prevented the GABA- and muscimol effects, while 2-hydroxysaclofen failed to antagonize them. In the longitudinal and circular layers of the proximal ileum, muscimol (100 microM) exerted a 'GABA-like' transient contractile effect, while baclofen (100 microM) did not elicit any response. Bicuculline, atropine and tetrodotoxin antagonized the GABA- and muscimol-induced contractile responses of longitudinal and circular layers, while 2-hydroxysaclofen was ineffective. The results suggested that the inhibitory and/or excitatory action of GABA on cholinergic transmission in different regions of cat ileum varies along an increasing gradient towards the terminal ileum and is mediated by GABA(A) and GABA(B) receptors in the terminal and distal ileum and by GABA(A) receptors in the proximal ileum.

Acetylcholinesterase↗

beta(1)-Adrenoceptors compensate for beta(3)-adrenoceptors in ileum from beta(3)-adrenoceptor knock-out mice.

1. This study examines beta(1)-, beta(2)- and beta(3)-adrenoceptor (AR)-mediated responses, mRNA levels and radioligand binding in ileum from beta(3)-AR knock-out (-/-) (KO) and wild type (+/+) (FVB) mice. 2. In KO and FVB mice, SR59230A (100 nM) (beta(3)-AR antagonist) antagonized responses to (-)-isoprenaline in both KO and FVB mice. (-)-Isoprenaline mediated relaxation of ileum was antagonized weakly by ICI118551 (100 nM) (beta(2)-AR antagonist). Responses to (-)-isoprenaline were more strongly antagonized by CGP20712A (100 nM) (beta(1)-AR antagonist), propranolol (1 microM) (beta(1)-/beta(2)-AR antagonist), carvedilol (100 nM) (non-specific beta-AR antagonist), and CGP12177A (100 nM) (beta(1)-/beta(2)-AR antagonist) in ileum from KO than in FVB mice. 3. Responses to CL316243 (beta(3)-AR agonist) in ileum from FVB mice were antagonized by SR59230A (100 nM) but not by propranolol (1 microM) or carvedilol (100 nM). CL316243 was ineffective in relaxing ileum from KO mice. 4. CGP12177A had no agonist actions in ileum from either KO or FVB mice. 5. beta(1)-AR mRNA levels were increased 3 fold in ileum from KO compared to FVB mice. This was associated with an increased maximum number of beta(1)-/beta(2)-AR binding sites (B(max)). beta(2)-AR mRNA levels were unaffected while no beta(3)-AR mRNA was detected in KO mice. 6. In mouse ileum, beta(3)-ARs and to a lesser extent beta(1)-ARs are the predominant adrenoceptor subtypes mediating relaxation in ileum from FVB mice. In KO mice beta(1)-ARs functionally compensate for the lack of beta(3)-ARs, and this is associated with increased beta(1)-AR mRNA and levels of binding.

Adrenergic beta-Agonists↗

Tetrahydrobiopterin regulates cyclic GMP-dependent electrogenic Cl- secretion in mouse ileum in vitro.

1. Basal electrogenic Cl- secretion, measured as the short-circuit current (Isc), was variable in ileum removed from tetrahydrobiopterin (BH4)-deficient hph-1 mice and wild-type controls in vitro, although values were not significantly different. 2. The basal nitrite release and mucosal cyclic guanosine 3',5'-monophosphate (cyclic GMP) production were similar in control and BH4-deficient ileum. 3. Mucosally added Escherichia coli heat-stable toxin (STa, 55 ng ml-1) increased the nitrite release, cyclic GMP levels and the Isc in control ileum, but its secretory actions were reduced in BH4-deficient ileum. 4. L-Arginine (1 mM) increased the nitrite release, cyclic GMP production and the Isc in control ileum, but the actions were reduced in BH4-deficient ileum. 5. Serosal carbachol (1 mM) stimulated maximum short-circuit currents of similar magnitude in both control and BH4-deficient ileum, whilst nitrite release and cyclic GMP production were minimal. 6. E. coli STa and L-arginine increased electrogenic Cl- secretion across intact mouse ileum in vitro by releasing nitric oxide and elevating mucosal cyclic GMP. The inhibition of these processes in the hph-1 mouse ileum suggests that BH4 may be a target for the modulation of electrogenic transport, and highlight the complexity of the interactions between nitric oxide and cyclic GMP in the gut.

Animals↗