Ileal Muscle Research Articles

Effects of hydralazine on responses to histamine and caffeine in ileal longitudinal muscle and taenia coli of the guinea pig

1. 1. The mechanism of tension inhibitory effects on histamine and caffeine-induced responses by hydralazine were studied in the ileal longitudinal muscle and taenia coli of the guinea-pig. Hydralazine, 10 −4 to 3 × 10 −3 M, inhibited both the tonic response and the increase in Ca uptake by the lanthanum (La) method evoked by histamine (10 −5 M) without affect on Ca efflux, with smaller effects on the phasic response in ileal muscle. 2. 2. Hydralazine suppressed caffeine- and IP 3-induced contractions after loading with Ca 2+ into the storage sites in saponin-treated fibers. However, hydralazine suppressed the caffeine- and IP 3-induced contractions in the skinned fibers relatively less than both the transient response to caffeine and phasic response to histamine in intact muscles, respectively. 3. 3. It is probable that hydralazine reduces the tonic response to histamine mainly by inhibiting Ca 2+ influx through receptor operated Ca 2+ channels in the ileum. In addition, hydralazine also decreases caffeine- or IP 3-induced Ca 2+ release from storage sites.

Adrenergic denervation hypersensitivity in ileal circular smooth muscle after small bowel transplantation in rats.

Effects of small bowel transplantation (SBT) on ileal motility are unknown. The aim of the present study was to investigate changes in spontaneous contractile activity and sensitivity to cholinergic and adrenergic agents in the ileal circular muscle after SBT in rats. Orthotopic SBT was performed in syngeneic rats to avoid immune phenomena. Distal ileal circular muscle strips from rats one week (N = 10) and eight weeks (N = 10) after SBT were stretched to optimal length (Lo), and basal spontaneous activity at Lo was measured. Dose-response experiments to the cholinergic agonist bethanechol (Be, 10(-8)-10(-4) M) were performed in the presence of tetrodotoxin (TTX, 10(-6) M) and to the adrenergic agonist norepinephrine (NE, 10(-8)-10(-4) M) with or without TTX. ED50 (negative log of drug-concentration that induced 50% effect) was calculated. We also studied rats with selective jejunoileal ischemia/ reperfusion, intestinal transection/reanastomosis, naive controls, and sham operated controls (N > or = 8/group). Spontaneous basal activity did not differ among groups. Sensitivity to Be was not different in rats after SBT or in other groups compared to control tissue. After SBT, hypersensitivity to NE was shown by a significant increase of ED50 at one and eight weeks after SBT (5.1 +/- 0.3 vs 6.2 +/- 0.4 and 6.2 +/- 0.2, respectively; P < 0.05) regardless of the presence of TTX. No hypersensitivity was observed after ischemia-reperfusion intestinal transection-reanastomosis, or sham operation. It is concluded that ileal hypersensitivity to NE was related to the extrinsic denervation obligated by the transplantation procedure, possibly mediated through an increase in number of receptors on smooth muscle, not on the enteric nerves.

O-29 - The tension development and glucose transport evoked by Mn2+ in both Ca2+- and Na+-deficient isotonic high-K+ medium in ileal muscle

O-29 - The tension development and glucose transport evoked by Mn2+ in both Ca2+- and Na+-deficient isotonic high-K+ medium in ileal muscle

CP2289, a new 5-HT3 receptor ligand: agonistic activities on gastroenteric motility.

A new 5-HT3 receptor ligand, CP2289, was synthesized and pharmacologically tested. Although CP2289 inhibited the Bezold-Jarisch reflex, it contracted the excised ileal muscle of mice, rats and guinea pigs. This response may reflect a partial agonist character of CP2289 in the gut. In vivo antiemetic and gastric emptying tests gave similar results.

Relaxant effect of xenin on rat ileum is mediated by apamin-sensitive neurotensin-type receptors

The action of xenin, a novel 25-residue peptide of the neurotensin (NT)/xenopsin family, was investigated in isolated rat ileal muscle strips and in dispersed longitudinal smooth muscle cells of rat small intestine in vitro. Xenin relaxes KCl-precontracted ileal strips dose dependently (1 nM-3 microM). The order of potency of the investigated peptides was as follows: xenopsin = NT = xenin > neuromedin N. Kinetensin was inactive. Tetrodotoxin, hexamethonium, tetraethylammonium, 4-aminopyridine, and NG-nitro-L-arginine did not influence the relaxant effects of xenin or NT, whereas the K+ channel blocker apamin nearly abolished their effects. Desensitization against one of the peptides or blockade of NT receptors by SR-48692 prevented the effect of xenin and NT. Structure-activity experiments revealed that the COOH-terminal part of the molecules of xenin and NT is essential for biological activity. Experiments with isolated dispersed smooth muscle cells and binding studies on intestinal smooth muscle cell membranes confirmed and extended the results obtained with muscle strips. In conclusion, xenin relaxes rat ileal smooth muscle via a muscular NT-type apamin-sensitive receptor.

Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre leaves.

Extracts containing gymnemic acids, which were extracted from the leaves of Gymnema sylvestre (GS) as nine fractions, were evaluated for their effects on a high K(+)-induced contraction of guinea-pig ileal longitudinal muscles, on glucose transport mediated by the difference of glucose-evoked transmural potential difference (delta PD) in the inverted intestine of guinea-pig and rat, and on blood glucose in rat. Among nine fractions obtained by high performance liquid chromatography from the extract, f-2 and f-4 strongly suppressed the high K(+)-induced contraction of the ileal muscle, f-3 and f-5 did so moderately, and f-8 and f-9 did so weakly, whereas the other fractions did not affect it. The degree of suppression of high K(+)-induced contraction by f-2 at 74% was almost the same as that of f-4 at 67%, at concentrations of 0.1 mg/ml. The suppressed contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The delta PD increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat were equally suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose tolerance test, f-2 and f-4 suppressed the elevation of blood glucose level. Both f-2 and f-4 suppressed the contraction of guinea-pig ileal longitudinal muscle, interfered with the increase in delta PD induced by glucose in the inverted intestines of guinea-pig and rat, and inhibited the elevation of blood glucose level. In conclusion, it is suggested that some of the extracts containing gymnemic acids from GS leaves suppress the elevation of blood glucose level by inhibiting glucose uptake in the intestine.

Decreased ileal muscle contractility and increased NOS II expression induced by lipopolysaccharide.

This study was designed to determine if an increase in nitric oxide synthase (NOS) activity induced by lipopolysaccharide (LPS) is associated with increases in NOS II protein and mRNA abundance and with altered ileal longitudinal muscle contractility. Strips of muscle taken from LPS-treated, but not control, animals exhibited reduced in vitro contractility when L-arginine was a component of the physiological salt solution. This reduction was reversed by N omega-nitro-L-arginine (L-NNA), a competitive inhibitor of NOS. Full-thickness segments of jejunum, ileum, and colon taken 5 h after LPS injection exhibited increased NOS activity, NOS II immunoreactivity, and NOS II mRNA abundance. Increased NOS II immunoreactivity and mRNA abundance also were detected in ileal muscle strips taken from LPS-treated animals. These data confirm the reported effects of LPS on intestinal NOS activity and indicate that it can be attributed, at least in part, to an increase in NOS II mRNA and protein abundance. Furthermore, the data suggest that an LPS-induced increase in NOS II may lead to a decrease in ileal muscle contractility.

Dantrolene blocks the tonic contraction and calcium influx evoked by K + in real longitudinal smooth muscle

1. 1. Dantrolene (10 −8-10 −4M) reduced the K + (60 mM) tonic response in accordance with decreased Ca 2+ uptake, as determined by La method, more than the phasic in ileal muscle. 2. 2. After saponin-treatment of the fibers, which leaves the Ca 2+ storage sites intact, dantrolene had only a slight effect on the caffeine-induced contraction. In Triton-X-100-treated fibers, in which the Ca 2+ release sites are destroyed, dantrolene did not affect the Ca 2+-induced contraction. 3. 3. The results suggest that dantrolene inhibited the high-K +-induced tonic response mainly by inhibiting Ca 2+ influx via voltage-dependent Ca 2+ channels in ileum without affecting contractile elements. In contrast, dantrolene had only a slight effect on the intracellular Ca 2+ release from caffeine-sensitive release sites.

The ileopsoas tunnel, a new antireflux technique for ureteroileal reimplantation: an experimental study in dogs.

A new antirefluxing ureteroileal anastomosis is described in which the implanted ureter is placed between the ileal segment and psoas muscle. The procedure was studied in eight experimental dogs, which were observed for 20 weeks. Radiologic and bacteriologic examinations, necropsy assessment and histopathologic results provided evidence that this ileo-psoas tunnel technique allows a unidirectional, non-obstructed flow of urine. The technique could be applied when ileal replacement of the ureter is necessary or in association with continent bladder replacement.

Assessment of antihistaminic and antimuscarinic effects of optical isomers of ephedrine and methylephedrine by receptor binding assay in guinea pig ileal muscle.

Effects of optical isomers of ephedrine (EPH) and methylephedrine (MEP) on histamine H1-receptors and muscarinic receptors in guinea pig ileal muscle were investigated by radioligand binding assay and by measuring the mechanical response to histamine and acetylcholine. EPH and MEP inhibited the specific binding of [3H]mepyramine and [3H]quinuclidinyl benzilate (QNB) to microsomal fractions prepared from this tissue. The rank order of inhibitory potency of [3H]mepyramine and [3H]QNB binding was d-->l-isomer and l-->d-isomer, respectively. Furthermore, the rank order of antagonistic potency in the mechanical response study was the same as that in the binding study. d-MEP competitively antagonized histamine-induced contraction (pA2 value; 5.14). These results suggest that each isomer of EPH and MEP has a distinct affinity for histamine H1-receptors and muscarinic receptors in guinea pig ileal muscle. The antihistaminic and antimuscarinic activity of these compounds may be largely attributed to competition at receptor sites. In addition, it is suggested that d-MEP exhibits a competitive antagonist activity for the histamine H1-receptor.

266 Senktide attenuates scopolamine-induced impairment of spontaneous alternation performance in mice

To test the hypothesis that different neurokinin receptors might be involved in the generation of either phasic or tonic muscular activity, selective ligands for the 6 neurokinin-1-receptor, [Sar9, Met(O2)]-SP, the neurokinin-2-receptor, [Nle10]-NKA4–10, and the neurokinin-3 receptor, [βAsp4,MePhe7]-NKB4–10, were used to evaluate the excitatory effects of these agonists in the longitudinal rat ileal muscle in vitro. The excitatory effect was analyzed as total response (area under the curve) and as tonic or phasic (area under or within the peaks) activity. Substance P (SP, relative amount of phasic activity in comparison to total activity: 3 × 10−8 M 87%, 3×10−6 M 30%) and the neurokinin-2-receptor selective agonist [Nle10]-NKA4–10 (N-NKA: 3×10−8 M 67%, 3 × 10−6 M 59%) caused both tonic and phasic responses, with the percentage of phasic responses decreasing at higher concentrations. The neurokinin-1-receptor selective agonist [βAla4, Sar9, Met(O2)]-SP4–11 caused a predominantly tonic response with only a small phasic component (10−8 M 27.1% 10−6 M 13.8%). The selective neurokinin-3 receptor agonist [βAsp4, MePhe7]-NKB4–10 caused a predominantly phasic motor response (SM-SP: 3 × 10−8 M 98%, 3 × 10−6 M 87%). Tetrodotoxin (TTX 10−6 M), omega-conotoxin (CTX 10−7 M) and atropine (10−6 M) had no significant influence on the contractile responses to all four peptides, indicating a direct action on the smooth muscle cell. Nitrendipine (10−7 M) and Ca2+-free medium significantly reduced phasic and tonic activity in response to all peptides. This showed the important role of the influx of extracellular calcium on the contractile process.These data demonstrated that phasic and tonic activity could be induced via a postsynaptic mechanism with selective neurokinin analogues. The NK-3 selective ligand produced phasic activity, whereas the NK-1 selective ligand produced tonic activity. This suggests that different neurokinin receptor subtypes are present on the smooth muscle cell which can elicit these different contractile responses.

Dantrolene blocks the tonic contractions to carbachol and histamine with smaller effects on the phasic due to release of intracellular Ca 2+ in ileal longitudinal muscle

1. 1. Dantrolene (10 −5-10 −4 M) inhibited carbachol- or histamine-induced tonic response according to the decrease in Ca 2+ uptake as determined by La method more than the phasic response in ileal muscle. However, dantrolene further reduced the second phasic response to sequential application of carbachol or histamine. 2. 2. After saponin-treatment of the fibres, which leaves the Ca 2+ storage sites intact, dantrolene had no effect on the IP 3-induced contraction. 3. 3. The results suggest that dantrolene inhibited the carbachol- or histamine-induced tonic response mainly by inhibiting Ca 2+ influx through receptor operated Ca 2+ channels in ileum with only slight effect on the intracellular Ca 2+ release from the storage sites. However, when dantrolene was continuously present, dantrolene might reduce a part of the Ca 2+ supply into the Ca 2+ storage sites.

Mechanism of action of somatostatin on the canine ileal circular muscle

The aim of this study was to investigate the mechanism of action of somatostatin on the circular muscle of the isolated canine ileum using the microelectrode technique. The membrane potential from circular muscle cells was recorded in two preparations: 1) whole thickness circular and longitudinal muscle (with intact myenteric and deep muscular plexuses, n = 13) and 2) isolated circular muscle (with only deep muscular plexus, n = 9). In this preparation, inhibitory junction potentials (IJPs), elicited after field stimulation, are mediated by a nitric oxide-related (NO-R) compound. Somatostatin (10(-6) M) transiently (2-5 min) depolarized the circular muscle cells in both whole thickness (3.6 +/- 1.0 mV, P < 0.01) and isolated circular muscle preparations (8.0 +/- 0.8 mV, P < 0.01). Somatostatin did not reduce either the amplitude or duration of the IJP in the isolated circular muscle but reduced slow-wave amplitude. In contrast, a reduction (20-50%) in the amplitude of the IJP was observed in the whole thickness preparation, and there was little effect on slow-wave amplitude. Somatostatin did not affect the induced slow wave observed in the whole thickness preparation after field stimulation. Apamin significantly reduced the amplitude of the IJP in both preparations. Somatostatin (10(-6) M) did not modify the apamin-resistant IJP. A reduction in the slow-wave amplitude was observed in the isolated circular muscle preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

Contractile activity and levels of cGMP and cAMP of prairie dog gallbladder and ileal muscle in response to S-nitroso-N-acetylpenicillamine (SNAP)

Contractile activity and levels of cGMP and cAMP of prairie dog gallbladder and ileal muscle in response to S-nitroso-N-acetylpenicillamine (SNAP)

Effect of hydrogen peroxide on guinea-pig ileal longitudinal smooth muscle contractility

Effect of hydrogen peroxide on guinea-pig ileal longitudinal smooth muscle contractility

Cholesterol rich liposome impairs gallbladder and ileal muscle cell contraction

Cholesterol rich liposome impairs gallbladder and ileal muscle cell contraction

Manganese ions induce tonic contraction after relaxation in a high-K+ medium in ileal longitudinal smooth muscle of guinea-pig.

In ileal longitudinal muscle 5 mM Mn2+ inhibited completely the K+ (60 mM)-induced tonic tension to the base line; however, the tension progressively increased to above the level of original tonic response evoked by K+ after 3 h in the presence of Mn2+. Tetrodotoxin 5 x 10(-5) M) had no influence on the tension development in the presence of Mn2+ in the high-K+ medium. Mn2+ also increased the tension in a high-K+, Ca(2+)-free medium. The Ca2+ antagonist, gallopamil (10(-6) M) inhibited the development of tension in the presence of Mn2+ in the high-K+ medium. The 45Ca uptake determined by the lanthanum method remained unchanged from control levels after 3 h of the 5 mM Mn2+ application in the high-K+ medium in spite of the development of the tension. The manganese uptake in the high-K+ medium, increased in accordance with the increase of duration of 5 mM Mn2+ application. Gallopamil inhibited manganese uptake in the high-K+ medium. These results suggest that Mn2+ firstly reduces K(+)-induced tension by inhibition of Ca2+ influx, subsequently, Mn2+ ions accumulate in the intracellular compartments through voltage-operated Ca2+ channels and may activate contractile proteins in the ileal muscle.

P-94 - Potentiation by neurotensin of carbachol-induced tension development in Ca2+-free solution in skinned guinea-pig ileal muscle.

P-94 - Potentiation by neurotensin of carbachol-induced tension development in Ca2+-free solution in skinned guinea-pig ileal muscle.

Differential effects of selective neurokinin agonists on phasic and tonic activity in rat ileal longitudinal muscle

To test the hypothesis that different neurokinin receptors might be involved in the generation of either phasic or tonic muscular activity, selective ligands for the 6 neurokinin-1-receptor, [Sar 9, Met(O 2)]-SP, the neurokinin-2-receptor, [Nle 10]-NKA 4–10, and the neurokinin-3 receptor, [βAsp 4,MePhe 7]-NKB 4–10, were used to evaluate the excitatory effects of these agonists in the longitudinal rat ileal muscle in vitro. The excitatory effect was analyzed as total response (area under the curve) and as tonic or phasic (area under or within the peaks) activity. Substance P (SP, relative amount of phasic activity in comparison to total activity: 3 × 10 −8 M 87%, 3×10 −6 M 30%) and the neurokinin-2-receptor selective agonist [Nle 10]-NKA 4–10 (N-NKA: 3×10 −8 M 67%, 3 × 10 −6 M 59%) caused both tonic and phasic responses, with the percentage of phasic responses decreasing at higher concentrations. The neurokinin-1-receptor selective agonist [βAla 4, Sar 9, Met(O 2)]-SP 4–11 caused a predominantly tonic response with only a small phasic component (10 −8 M 27.1% 10 −6 M 13.8%). The selective neurokinin-3 receptor agonist [βAsp 4, MePhe 7]-NKB 4–10 caused a predominantly phasic motor response (SM-SP: 3 × 10 −8 M 98%, 3 × 10 −6 M 87%). Tetrodotoxin (TTX 10 −6 M), omega-conotoxin (CTX 10 −7 M) and atropine (10 −6 M) had no significant influence on the contractile responses to all four peptides, indicating a direct action on the smooth muscle cell. Nitrendipine (10 −7 M) and Ca 2+-free medium significantly reduced phasic and tonic activity in response to all peptides. This showed the important role of the influx of extracellular calcium on the contractile process. These data demonstrated that phasic and tonic activity could be induced via a postsynaptic mechanism with selective neurokinin analogues. The NK-3 selective ligand produced phasic activity, whereas the NK-1 selective ligand produced tonic activity. This suggests that different neurokinin receptor subtypes are present on the smooth muscle cell which can elicit these different contractile responses.

Purinergic modulation of spontaneous activity and of responses to high potassium and acetylcholine in rat ileal smooth muscle

1. In rat ileal smooth muscle both adenosine and ATP at 10(-4) M significantly enhanced spontaneous mechanical activity. The excitatory actions of adenosine were blocked by the P1 receptor antagonist 8-phenyltheophylline and the excitatory effects of ATP were significantly reduced by the P2 receptor antagonist quinidine. 2. The P2 receptor desensitizer alpha,beta-methylene-ATP was without effect on ACh responses nor did the stable analogue beta,gamma-methylene-ATP exert any effect on spontaneous mechanical activity. 3. Pretreatment with adenosine caused a dose-dependent enhancement of K-induced contractures in the ileum. Low adenosine concentrations slightly inhibited and high concentrations slightly enhanced ACh-induced contractures in the ileum. 4. ATP potentiated the phasic component of the ileal K-induced contracture but strongly inhibited tonic force at high concentrations. This agent slightly inhibited the phasic component of the ACh-induced contracture while strongly inhibiting ACh-induced tonic force. 5. alpha,beta-methylene-ATP inhibited ileal muscle ACh induced contractures while it potentiated both phasic and tonic K-induced contractures. beta,gamma-methylene ATP inhibited ACh-induced contractures but it enhanced K-induced phasic contractures while inhibiting K-induced tonic force. 6. The results of this study suggest that rat ileum may contain the A1 subtype of the P1 receptor but the evidence for a P2 receptor subtype is conflicting despite the inhibition of ATP actions by quinidine. 7. The inhibition of K- and ACh-induced tonic force suggests that adenosine and ATP interactions with ileal smooth muscle may inactivate slow voltage-dependent calcium channels leading to EC uncoupling.