α- and β-Adrenergic receptor mechanisms in spontaneous contractile activity of rat ileal longitudinal smooth muscle

Gastrointestinal motility is influenced by adrenergic modulation. Our aim was to identify specific subtypes of adrenergic receptors involved in inhibitory mechanisms that modulate gut smooth muscle contractile activity. Muscle strips of rat ileal longitudinal muscle were evaluated for spontaneous contractile activity and for equimolar dose-responses (10-7 to 3 x 10-5 M) to the adrenergic agents norepinephrine (nonselective agonist), phenylephrine (α1-agonist), clonidine (α2-agonist), prenalterol (β1-agonist), ritodrine (β2- agonist), and ZD7114 (β3-agonist) in the presence and absence of tetrodotoxin (nonselective nerve blocker). Norepinephrine (3 x 10-5 M) inhibited 65 ± 6% (mean ± SEM) of spontaneous contractile activity. The same molar dose of ritodrine, phenylephrine, or ZD7114 resulted in less inhibition (46 ±7%, 31 ± 5%, and 39 ± 3%, respectively; P < 0.05). The calculated molar concentration of ZD7114 needed to induce 50% inhibition was similar to that of norepinephrine, whereas higher concentrations of phenylephrine or ritodrine were required. Clonidine and prenalterol had no effect on contractile activity. Blockade of intramural neural transmission by tetrodotoxin affected the responses to ritodrine and phenylephrine (but not to norepinephrine or ZD7114), suggesting that these agents exert part of their effects via neurally mediated enteric pathways. Our results suggest that adrenergic modulation of contractile activity in the rat ileum is mediated primarily by muscular β3-, β2-, and α1 -receptor mechanisms; the latter two also involve neural pathway

Role of Selective α and β Adrenergic Receptor Mechanisms in Rat Jejunal Longitudinal Muscle Contractility

Gut motility is modulated by adrenergic mechanisms. The aim of our study was to examine mechanisms of selective adrenergic receptors in rat jejunum. Spontaneous contractile activity of longitudinal muscle strips from rat jejunum was measured in 5-ml tissue chambers. Dose-responses (six doses, 10−7-3 × 10−5M) to norepinephrine (NE, nonspecific), phenylephrine (PH, α1), clonidine (C, α2), prenalterol (PR, β1), ritodrine (RI, β2), and ZD7714 (ZD, β3) were evaluated with and without tetrodotoxin (TTX, nerve blocker). NE(3 × 10−5M) inhibited 74 ± 5% (mean ± SEM) of spontaneous activity. This was the maximum effect. The same dose of RI(β2), PH(α1), or ZD(β3) resulted in an inhibition of only 56 ± 5, 43 ± 4, 33 ± 6, respectively. The calculated concentration to induce 50% inhibition (EC50) of ZD(β3) was similar to NE, whereas higher concentrations of PH(α1) or RI(β2) were required. C(α2) and PR(β1) had no effect. TTX changed exclusively the EC50 of RI from 4.4 ± 0.2 to 2.7 ± 0.8% (p < 0.04). Contractility was inhibited by NE (nonspecific). PH(α1), RI(β2), and ZD(β3) mimic the effect of NE. TTX reduced the inhibition by RI. Our results suggest that muscular α1, β2, and β3 receptor mechanisms mediate adrenergic inhibition of contractility in rat jejunum. β2 mechanisms seem to involve also neural pathway

Role of selective alpha and beta adrenergic receptor mechanisms in rat jejunal longitudinal muscle contractility

Gut motility is modulated by adrenergic mechanisms. The aim of our study was to examine mechanisms of selective adrenergic receptors in rat jejunum. Spontaneous contractile activity of longitudinal muscle strips from rat jejunum was measured in 5-ml tissue chambers. Dose-responses (six doses, 10(-7) -3 x 10(-5)M) to norepinephrine (NE, nonspecific), phenylephrine (PH, alpha1), clonidine (C, alpha2), prenalterol (PR, beta1), ritodrine (RI, beta2), and ZD7714 (ZD, beta3) were evaluated with and without tetrodotoxin (TTX, nerve blocker). NE(3 x 10(-5)M) inhibited 74 +/- 5% (mean +/- SEM) of spontaneous activity. This was the maximum effect. The same dose of RI(beta2), PH(alpha1), or ZD(beta(3)) resulted in an inhibition of only 56 +/- 5, 43 +/- 4, 33 +/- 6, respectively. The calculated concentration to induce 50% inhibition (EC50) of ZD(beta3) was similar to NE, whereas higher concentrations of PH(alpha1) or RI(beta2) were required. C(alpha2) and PR(beta1) had no effect. TTX changed exclusively the EC50 of RI from 4.4 +/- 0.2 to 2.7 +/- 0.8% (p < 0.04). Contractility was inhibited by NE (nonspecific). PH(alpha1), RI(beta2), and ZD(beta3) mimic the effect of NE. TTX reduced the inhibition by RI. Our results suggest that muscular alpha1, beta2, and beta3 receptor mechanisms mediate adrenergic inhibition of contractility in rat jejunum. beta2 mechanisms seem to involve also neural pathways

Role of beta1-, beta2-, and beta3-adrenoceptors in contractile hypersensitivity in a model of small bowel transplantation

BACKGROUND: Chronic extrinsic denervation induced by small bowel transplantation (SBT) results in adrenergic hypersensitivity in rat ileum. This study evaluated the role of neuronal and/or muscular beta1-, beta2-, and beta3-adrenoceptor (AR) mechanisms on contractility. METHODS: Ileal longitudinal muscle strips from Lewis rats (n = 6 rats per group, 8 strips per rat): naive controls (NC), 4 months after sham operation (SC) or after syngeneic orthotopic SBT were studied in vitro. Spontaneous contractile activity and dose responses (10(-8)-10(-4) mol) to isoprenaline (IP), a nonspecific beta-AR agonist were studied with or without selective antagonists (10(-5) mol), for beta1- (atenolol), beta2- (ICI 118551), or beta3- (SR 59230A) AR subtypes in the presence or absence of tetrodotoxin (TTX; 10(-6) mol; nerve blocker). RESULTS: pEC50 (neg log of EC50, which is the concentration where 50% of inhibition was observed) of IP was 7.2 +/- 0.2 (mean value +/- SEM) in SBT vs 6.3 +/- 0.1 in SC and 6.3 +/- 0.2 in NC (both P < .05 vs SBT), reflecting adrenergic hypersensitivity. Beta1- and beta2-AR blockade induced a TTX-sensitive right shift of the curve only in SBT and normalized pEC50 values from 7.2 +/- 0.2 to 6.4 +/- 0.1 and 7.2 +/- 0.2 to 6.6 +/- 0.1, respectively (P < .05). Beta3-AR blockade shifted the curve independent of the presence of TTX to the right in all groups (all P < .05). CONCLUSIONS: In rat ileum, adrenergic inhibition of contractility was dependent on muscular beta3-AR pathways, whereas posttransplant hypersensitivity was due to upregulated neuronal beta1- and beta2-AR mechanisms that were inactive before SBT

Serological and DNA-based evaluation of Chlamydia pneumoniae infection in inflammatory bowel disease

OBJECTIVES: Chlamydia has been associated with autoimmune diseases, but a link between chlamydial infection and the aetiopathogenesis of inflammatory bowel disease (IBD) remains controversial. In this study we assessed the relationship between chlamydial infection and IBD, as evidenced by serological measurement and DNA analysis of mucosal biopsy specimens. PATIENTS AND METHODS: The sera of 78 patients with Crohn's disease (CD), 24 patients with ulcerative colitis (UC), 73 healthy family members, and 20 healthy controls were tested for anti-C. pneumoniae IgG titres. A subgroup consisting of 13 UC and 39 CD patients was screened for the presence of chlamydial DNA on 42 inflamed versus 30 non-inflamed biopsy specimens and for mutations of their NOD2/CARD15 gene. RESULTS: Anti-C. pneumoniae IgG antibodies were found in the sera of 32 (41%) patients with CD, 11 (46%) patients with UC, 35 (48%) of unaffected family members, and nine (45%) unrelated healthy controls. Thirty-five percent of the control, 18% CD and 24% UC biopsy specimens contained C. pneumoniae DNA. In CD, however, C. pneumoniae DNA was significantly more frequently found in inflamed (27%) versus non-inflamed (8%) biopsy specimens (P < 0.05, Fisher's exact test). The frequencies of NOD2/CARD15 mutations were 33% for CD patients with C. pneumoniae DNA compared to 47% for CD patients without C. pneumoniae DNA. CONCLUSION: We found no marked differences in respect to anti-C. pneumoniae serum IgG or C. pneumoniae DNA between healthy controls and patients with IBD. However, in CD patients, inflamed tissue specimens contained significantly more likely C. pneumoniae DNA compared with biopsies from unaffected areas. Thus C. pneumoniae is unlikely to be of pathogenic importance in IBD while it may still influence local clinical manifestations

Professor of Surgery, Gastroenterology Research Unit (AL 2-435) Mayo Clinic

Abstract Pancreatoduodenectomy may be a difficult operation, not only during the resectional part of the procedure, but also during reconstruction. Usually, these problems are due to local conditions of the organs/tissues, such as small diameter of the common bile duct or pancreatic duct, friable soft pancreas, vascular anomalies, etc. Reconstruction may also be problematic because of the hemodynamic instability of the patient during surgery (subsequent to massive hemorrhage), and in those unusual cases, delayed reconstruction may be a life-saving, wise choice