Atropisomerism in 3-arylthiazolidine-2-thiones. A combined dynamic NMR and dynamic HPLC study.

Sterically hindered 3-arylthiazolidine-2-thiones were prepared by a solvent-free reaction with arylisothiocyanates and 1,4-dithiane-2,5-diol. Atropisomerism was observed in two compounds (3 and 4, aryl = 1-naphthyl and 2-methylnaphth-1-yl), whose rotational energy barriers were measured using dynamic NMR and dynamic HPLC. The experimental analyses were supported by DFT calculations. Thermally stable atropisomers were obtained by dehydration of compounds 3 and 4 and the absolute configuration of the atropisomers of compound 6 was determined by theoretical simulation of the ECD and VCD spectra.

Fulminant ectopic Cushing's syndrome caused by metastatic small intestine neuroendocrine tumour - a case report and review of the literature.

Cushing's syndrome (CS) secondary to adrenocorticotropic hormone (ACTH) producing tumours is a severe condition with a challenging diagnosis. Ectopic ACTH-secretion often involves neuroendocrine tumours (NET) in the respiratory tract. ACTH-secreting small intestine neuro-endocrine tumours (siNET) are extremely rare entities barely reported in literature. This review is illustrated by the case of a 75-year old woman with fulminant ectopic CS caused by a ACTH-secreting metastatic siNET. Severe hypokalemia, fluid retention and refractory hypertension were the presenting symptoms. Basal and dynamic laboratory studies were diagnostic for ACTH-dependent CS. Extensive imaging studies of the pituitary and thorax-abdomen areas were normal, while [68Ga]Ga-DOTATATE PET-CT revealed increased small intestine uptake in the left iliac fossa. The hypercortisolism was well controlled with somatostatin analogues, after which a debulking resection of the tumour was performed. Pathological investigation confirmed a well-differentiated NET with sporadic ACTH immunostaining and post-operative treatment with somatostatin analogues was continued with favourable disease control.

Chronic constipation in hypercalcemic patients with primary hyperparathyroidism.

BACKGROUND: Chronic constipation (C), among gastrointestinal symptoms, is commonly associated with primary hyperparathyroidism (PHPT) and probably attributable to hypercalcemia. OBJECTIVE OF THE STUDY: To evaluate in patients affected with PHPT the prevalence of C utilizing a validated questionnaire and the current prevalence of C compared to that observed in the past and to evaluate the relationship between C and the severity of PHPT. METHODS: 55 outpatients affected with PHPT, admitted to our Department of Internal Medicine and Medical Specialities in the years (2006-2009) were studied (group 1: 50 postmenopausal women and 5 men, mean age 61.9 +/- 9.4 years), together with 55 sex and age matched controls (group 2). Also considered were a group of PHPT patients observed, in the same ambulatory, during the years '70-'80 (group 3). A questionnaire, Rome II criteria, was administered and used to define C, whereas only anamneses were used to define C in group 3. RESULTS: The prevalence of C in patients with PHPT was 21.8% in group 1 vs 12.7% in group 2 (n.s.) and 32.7% in group 3. There is a decreasing trend in the prevalence of C in patients with PHPT as observed from 1970-89 to 2006-2009 (p < 0.05). The reduction of C was associated together with a significant reduction in the serum calcium level (p < 0.001). The presence of C vs its absence in patients with PHPT is characterized by higher values of calcemia (p < 0.001), ionized calcium (p < 0.001), and parathyroid hormone (p = 0.019). CONCLUSION: The actual prevalence of C in patients with PHPT is not significantly different from that found in the control group and is decreasing with respect to the past years. Moreover, C seems to be associated with the severity of the disease rather than with the diagnosis of PHPT per se.

A single-centre analysis of post-colonoscopy colorectal cancer.

PATIENTS AND METHODS: A prospective registration of patients with colorectal cancer and a colonoscopy within the last 10 years. We tried to classify these post-colonoscopy colorectal cancers (PCCRCs) by most reasonable explanation and into subcategories suggested by the World Endoscopy Organization (WEO) and calculated the unadjusted PCCRC rate. RESULTS: 47 PCCRCs were identified. The average age at diagnosis of PCCRC was 73 years. PCCRCs were more located in the right colon with a higher percentage of MSI-positive and B-RAF mutated tumours. The average period between index colonoscopy and diagnosis of PCCRC was 4.2 years. Sixty-eight % of all PCCRCs could be explained by procedural factors. The mean PCCRC-3y of our department was 2.46%. CONCLUSIONS: The data of our centre are in line with the data of the literature from which can be concluded that most postcolonoscopy colorectal cancers are preventable. The PCCRC-3y is an important quality measure for screening colonoscopy. Ideally all centres involved in the population screening should measure the PCCRC-3 y annually, with cooperation of the cancer registry and reimbursement data provided by the Intermutualistic Agency (IMA).

Supernatants of irritable bowel syndrome mucosal biopsies impair human colonic smooth muscle contractility.

BACKGROUND: Changes in intestinal motility are likely to contribute to irritable bowel syndrome (IBS) pathophysiology. The aim of the study was to investigate the effects of IBS mucosal supernatants on human colonic muscle contractility. METHODS: Supernatants were obtained from biopsies of 18 IBS patients-nine with constipation (IBS-C) and nine with diarrhea-predominant IBS (IBS-D)-and nine asymptomatic subjects, used as controls. Colonic circular smooth muscle strips or isolated cells (SMC) were exposed to control or IBS supernatants. Spontaneous phasic contractions on strips and morphofunctional parameters on cells were evaluated in basal conditions and in response to acetylcholine (Ach). Incubation with IBS supernatants was also conducted in the presence of antagonists and inhibitors (namely histamine, protease and prostaglandin antagonists, nuclear factor-kappa B inhibitor, catalase, NADPH oxidase inhibitor, and the cAMP- and/or cGMP-cyclase inhibitors). KEY RESULTS: Exposure to IBS-C and IBS-D supernatants induced a significant reduction in basal tone and Ach-elicited contraction of muscle strips and a significant shortening and impairment of Ach contraction of SMCs. The NADPH oxidase inhibitor prevented the effect of supernatants, while the protease antagonist only IBS-C effect. No effect was observed with the other antagonists and inhibitors. Dilution of IBS-D supernatants partially restored the effects only on SMCs, whereas dilution of IBS-C supernatants significantly reverted the effects on muscle strips and Ach-elicited response on SMC. CONCLUSIONS & INFERENCES: Supernatants from mucosal biopsies of IBS patients reduce colonic contractility. The observed impairment was concentration dependent, likely occurring through intracellular oxidative stress damage, involving different neuromotor mechanisms depending on the IBS subtype.

Vasoactive intestinal peptide receptor subtypes and signalling pathways involved in relaxation of human stomach.

Vasoactive intestinal peptide (VIP) relaxes smooth muscle by interacting with receptors coupled to cAMP- or cGMP-signalling pathways. Their relative contribution to human gastric relaxation is unknown. This study aimed at investigating, in terms of biological activity, receptor expression and related signalling pathways, the action of VIP separately on the human fundus and the antrum. VIP caused greater relaxation of smooth muscle cells (SMC) and strips of the antrum presenting on the former a higher efficacy and potency (ED(50): 0.53 +/- 0.17 nmol L(-1)) than on the fundus (ED(50): 3.4 +/- 1.4 nmol L(-1)). On both fundus and antrum strips, its effect was tetrodotoxin insentitive. Reverse transcriptase-polymerase chain reaction analysis showed the sole expression of VPAC2 and natriuretic peptide clearance receptors, with VPAC2 being more abundant in the antrum. Functional regional differences in receptor-related signalling pathways were found. Activation of the cAMP-pathway by forskolin or its inhibition by adenylate cyclase (2'5'-dideoxyadenosine) or kinase (Rp-cAMPs) inhibitors had more pronounced effects on antrum SMC. Activation of the cGMP-pathway by sodium nitroprusside or its inhibition by guanylate cyclase (LY83583) or kinase (KT5823) inhibitors had more effects on fundus SMC, on which a higher expression of endothelial nitric oxide synthase was found. In conclusion, regional differences in VIP action on human stomach are related to distinct myogenic properties of SMC of the antrum and the fundus.

Somatostatin receptor subtypes mediate contractility on human colonic smooth muscle cells.

This study demonstrates the expression of functional somatostatin receptor (sstr) subtypes in human circular and longitudinal colonic smooth muscle cells (SMC). Native somatostatin (SS) and sstr subtype-specific analogues were used to characterize the sstr subtypes present in both cell types by contraction/relaxation studies. Qualitative and quantitative mRNA analysis and immunohistochemistry of sstr subtypes were also carried out. sstr subtype 2 mRNA was expressed in circular SMC, and various levels of subtypes 1, 2 and 3 mRNA were expressed in longitudinal colonic SMC. Native SS and each subtype-specific analogue exerted a modest, but significant, contraction, although inhibition of carbachol-induced contraction (relaxation) was the main effect on SMC from both layers. CH-288, a sstr subtype 1-specific analogue, and octreotide, a sstr subtype 2-specific analogue, were the most effective relaxant analogues on longitudinal and circular SMC, respectively. sstr subtypes display a distinct expression pattern on human colonic SMC; on circular SMC, subtype 2 is the only sstr, whereas sstr subtypes 1, 2 and 3 are expressed on human SMC isolated from the longitudinal layer. The contractile effects of SS are mediated through sstr subtype 2 and sstr subtype 1 on circular and longitudinal human colonic SMC, respectively.

Regional differences in signalling transduction pathways among smooth muscle cells from rabbit colon.

Smooth muscle cells (SMC) from the circular muscle layer of rabbit colon, taken from the proximal and distal regions that are known to have different physiological and motor activities, were used to highlight distinct regional intrinsic myogenic properties and to investigate the correlations between receptor and signalling transduction pathways. Contractile agonists were shown to be more potent on proximal than on distal SMC in inducing contraction and intracellular Ca(2+) increase. Concentration-response curves of agonists-induced Ca(2+) increase were constantly shifted to the right, though remaining parallel, with respect to contraction curves, independently of the region analysed. Using agents activating different steps of cAMP-or cGMP-mediated intracellular cascades, main regional differences were revealed as far as relaxation was concerned. Relaxation of proximal SMC was found to be essentially cGMP mediated, while that of distal SMC was cAMP mediated. In conclusion, the motor patterns of the two regions appear to be influenced by distinct regional biochemical characteristics that are intrinsic to colonic SMC.

Effect of bombesin on plasma insulin, pancreatic glucagon, and gut glucagon in man.

The effect of bombesin on insulin, pancreatic glucagon, and gut glucagon was investigated in eight healthy volunteers and two pancreatectomized patients. Bombesin, infused iv at the constant rate of 5 ng kg-1 min-1, produced a sharp and statistically significant rise in the plasma insulin concentration. The peak was reached at 5 min (26 +/- 2.17 microU/ml; P less than 0.005 vs. basal values), followed by a prolonged and statistically significant (P less than 0.05) decrease in blood glucose. Pancreatic glucagon rapidly rose to a maximal value of 80.5 +/- 7.6 pmol/liter (P less than 0.005 vs. basal values). In contrast with the prompt increase in insulin and glucagon plasma levels, the peak in gut glucagon concentration (55.8 +/- 4.6 pmol/liter; P less than 0.005 vs. basal values) was reached 30 min after bombesin infusion was discontinued. In the two pancreatectomized patients, bombesin induced an increase in gut glucagon concentrations only. The results presented indicate that bombesin acts directly on the A and B cells of the pancreas, influencing glucose homeostasis; however, more complex mechanisms seem to be involved in gut glucagon secretion.

Bombesin effects on human GI functions.

In this article some of the actions of amphibian skin peptide Bombesin (BBS) on human gastrointestinal and pancreatic functions are reviewed. BBS causes increases of lower esophageal sphincter pressure, delay of gastric emptying, inhibition of mechanical activity of duodenum and jejunum and gallbladder emptying. BBS also releases in man gastrin and stimulates gastric acid secretion. BBS administration induces release of insulin, glucagon and pancreatic polypeptide from human Islet of Langerhans and causes secretion of pancreatic bicarbonates and enzymes in duodenal juice and release of pancreatic enzymes in blood stream.

The neuroendocrine control of gastrointestinal motor activity.

Here we describe interactions between peptide hormones and the enteric, autonomic and central innervation, and to the regulation of some major digestive events. The neuronal functions, the variety of neurochemically distinct neurons and some recent results on chemical marker combinations in the neurons are mentioned. A classification of the substances potentially acting as neurotransmitters or neuromodulators of gut motility is also reported. The major motor events taken into account include the migrating motor complex, the peristaltic reflex, the gastric emptying and the gallbladder/sphincter of Oddi relationships. The demonstration that numerous peptides may be detected in, and secreted by, the neurons has opened a fascinating area of study. Various difficulties hampering the comprehension of modalities according to which gastrointestinal motility is regulated, are discussed. Experimental evidence however, has to be considered cautiously. Expressions such as 'the peptidergic control of motility' may suggest that these peptides are the primary subjects in the strategy leading to the motor events, rather than the transmitters of impulses whose strategy is decided at higher levels. The autonomy of the peripheral regulatory system is apparent in certain conditions and has an important supplementary value. In general, however, the neuroendocrine regulation remains a global phenomenon testifying the unity of the living organism.

Evidence that bombesin releases extragastric gastrin in man.

Bombesin-induced gastrin release from extragastric sources has been investigated in two groups of patients without gastric antrum: 11 patients with total gastrectomy and 11 patients with subtotal (Billroth II) gastrectomy. A 30-min bombesin infusion (5 ng . kg-1 . min-1) caused a prompt significant gastrin increase (P less than 0.05) in both groups of patients. The gastrin response to bombesin was significantly (P less than 0.005) lower in patients without antral tissue than in the control group (n = 7). The individual peak gastrin responses, in totally (TG) and subtotally (SG) gastrectomized patients, were significantly over basal levels (TG: peak 100.3 +/- 12 vs. basal 62.8 +/- 9.1, P less than 0.005; SG: peak 96.9 +/- 9.4 vs. basal 72.4 +/- 6.8, P less than 0.001; pg/ml, mean +/- S.E.M.). These data indicate that bombesin acts not only on antral G cells, but on all gastrin cells in the gastrointestinal tract.

Contribution of NK3 tachykinin receptors to propulsion in the rabbit isolated distal colon.

The role of NK3 receptors in rabbit colonic propulsion has been investigated in vitro with the selective agonist, senktide, and two selective antagonists, SR142801 and SB222200. Peristalsis was elicited by distending a rubber balloon with 0.3 and 1.0 mL of water leading to a velocity of 2.2 and 2.8 mm s-1, respectively. At concentrations of 1 nM, senktide inhibited propulsion evoked by both distensions (range 25-40%), whereas at 6 and 60 nmol L-1 facilitated 'submaximal' propulsion by 30%. In the presence of Nomega-nitro-L-arginine (L-NNA, 200 micromol L-1), which per se caused a slight prokinetic effect, 1 nmol L-1 senktide markedly accelerated propulsion (range 35-50%). Hexamethonium (200 micromol L-1) had minor effects on propulsion. In its presence, 60 nmol L-1 senktide significantly inhibited propulsion induced by both stimuli (range 20-50%). SR142801 (0.3, 3 nmol L-1) and SB222200 (30, 300 nmol L-1) facilitated 'submaximal' propulsion (range 20-40%). Conversely, higher antagonist concentrations (SR142801: 30, 300 nM; SB222200: 1, 10 micromol L-1) inhibited propulsion to both distensions by 20%. A combination of SR142801 (300 nmol L-1) plus hexamethonium (200 micromol L-1) induced an approximately four-fold greater inhibition of propulsion than that induced by SR142801 alone. In conclusion, in the rabbit-isolated distal colon, a subset of NK3 receptors located on descending pathways mediates an inhibitory effect on propulsion by activating a NO-dependent mechanism. Another subset of NK3 receptors, located on ascending pathways mediates a facilitative effect involving a synergistic interaction with cholinergic nicotinic receptors.

Characterization of opioid receptors on isolated canine gallbladder smooth muscle cells.

Smooth muscle cells were isolated from the fundus of the canine gallbladder and examined for the presence of opioid receptors. The cells contracted in a concentration-dependent manner in response to three opioid peptides (Met-enkephalin, dynorphin1-13 and Leu-enkephalin), which are known derivatives of opioid precursors present in myenteric neurons of the gut. The order of potency was Met-enkephalin greater than dynorphin1-13 greater than Leu-enkephalin. The contractile response to opioid agonists was selectively inhibited by opioid antagonists (naloxone and Mr2266) but not by muscarinic, CCK/gastrin or tachykinin antagonists. Equivalent responses to the three opioid peptides exhibited differential sensitivity to preferential antagonists of mu (naloxone) and kappa (Mr2266) opioid receptors consistent with the presence of the three main types of opioid receptors (mu, delta and kappa) on canine gallbladder muscle cells.

Optimisation of isolation of richly pure and homogeneous primary human colonic smooth muscle cells.

BACKGROUND: Inherent properties of gastrointestinal smooth muscle can be assessed using isolated cell suspensions. Currently available isolation techniques, based on short 2-h enzymatic digestion, however, present the disadvantage of low cellular yield with brief viability. These features are an important limiting factor especially in studies in humans in which tissue may not be available daily and mixing of samples is not recommended. AIMS: To optimise the isolation procedure of cells from human colon to obtain a richly pure primary smooth muscle cell preparation. METHODS: Slices of circular muscle layer, obtained from surgical specimens of human colon, were incubated overnight in Dulbecco's modified eagle's medium supplemented with antibiotics, foetal bovine serum, an ATP-regenerating system and collagenase. On the following day, digested muscle strips were suspended in HEPES buffer, and spontaneously dissociated smooth muscle cells were harvested and used either immediately or maintained in suspension for up to 72 h. Cell yield, purity, viability, contractile responses, associated intracellular calcium signals and RNA and protein extraction were evaluated and compared to cell suspensions obtained with the current short digestion protocol. RESULTS AND CONCLUSION: The overnight isolation protocol offers the advantage of obtaining a pure, homogeneous, long-life viable cell suspension that maintains a fully differentiated smooth muscle phenotype unchanged for at least 72 h and that allows multiple functional/biochemical studies and efficient RNA extraction from a single human specimen.

Intracavitary cisplatin (CDDP) in the treatment of metastatic pericardial involvement from breast and lung cancer.

Seven patients with lung cancer and two with breast cancer developed a symptomatic pericardial effusion and were treated with intrapericardial cisplatin (CDDP). In all of the patients, cytological confirmation of metastatic effusion was achieved. A single cycle with 10 mg of cisplatin diluted in 20 ml of normal saline was administered for five consecutive days via an intrapericardial catheter. Control of recurrent effusions was obtained in eight of the nine patients. No significant side-effects were observed.

Role of endoscopic sphincterotomy of the minor papilla in pancreas divisum.

BACKGROUND: Pancreas divisum (PD) is a common anatomical variant of the pancreatic duct system. Only a little percentage of patients with this altered anatomy develop symptoms: acute recurrent pancreatitis (ARP), chronic pancreatitis (CP) and pancreatic-type pain alone. These have been supposed to arise from an obstruction to outflow of the pancreatic dorsal duct due to a stenosis of the minor papilla. Endoscopic sphincterotomy of the minor papilla (MiES) can be considered an effective treatment for patients with PD and ARP supported by stenosis or obstruction of the minor papilla. On the other hand, the access through the minor papilla is essential for therapeutic pancreatic endoscopy in patients with PD and CP, but the effectiveness of MiES in these patients is extremely controversial. MATERIALS AND METHODS: Aim of this brief review has been to evaluate the short and long-term effects of endoscopic pancreatic interventions in patients affected by symptomatic PD who underwent therapeutic endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic sphincterotomy of the minor papilla (MiES). The main literature database was Medline (1966-2013). RESULTS: Data come from a personal overview of articles emerging from the same search strategy. CONCLUSIONS: Nowadays, when endoscopic pancreatic drainage is indicated in patient with symptomatic PD, access through the minor papilla (MiP) is required. Therapeutic endoscopic interventions provide less invasive alternatives to the surgical approach.

Contribution of intestinal smooth muscle to Crohn's disease fibrogenesis.

Mesenchymal cells transdifferentiation and extracellular matrix deposition are involved in the fibrotic process of Crohn's disease (CD). Mesenchymal smooth muscle cells (SMCs) de-differentiation, driven by Platelet-derived growth factor (PDGF) that counteracts Transforming growth factor (TGF-ß) has been studied in vascular muscle. The role of SMCs in intestinal fibrogenesis is still not clearly elucidated. Aim of the study was to evaluate the possible myogenic contribution to CD fibrotic process through the comparative analysis of histological, morphometric and molecular alterations occurring in human smooth muscle. Full thickness specimens were obtained from CD (non-involved and stenotic tracts) and healthy (control) ileum. Tissues were processed for histological and immunohistochemical (IHC) analyses and SMCs were isolated from the muscularis propria for morphofunctional and molecular (qPCR) analyses. CD stenotic ileum showed a significant increased thickness of all layers compared to CD non-involved and control ileum. IHC revealed an overexpression of α-smooth muscle actin and collagens I-III throughout all intestinal layers only in stenotic tracts. The two growth factors, PDGF and TGF-ß, showed a progressive increase in expression in the muscle layer from CD non-involved to stenotic tracts. Freshly isolated SMCs presented alterations in CD non-involved tracts that progressively increased in the stenotic tracts consisting in a statistical increase in mRNA encoding for PDGF-ß and collagen III, paralleled to a decrease in TGF-ß and Tribbles-like protein-3 mRNA, and altered morphofunctional parameters consisting in progressive decreases in cell length and contraction to acetylcholine. These findings indicate that intrinsic myogenic alterations occur in CD ileum, that they likely precede stricture formation, and might represent suitable new targets for anti-fibrotic interventions.

Lactobacillus rhamnosus protects human colonic muscle from pathogen lipopolysaccharide-induced damage.

BACKGROUND: Lactobacillus species might positively affect gastrointestinal motility. These Gram-positive bacteria bind Toll-like receptor 2 (TLR2) that elicits anti-inflammatory activity and exerts protective effects on damage induced by lipopolysaccharide (LPS). Whether such effect occurs in gastrointestinal smooth muscle has not been established yet. Aim of this study was to characterize the effects of Lactobacillus rhamnosus GG (LGG) and of supernatants harvested from LGG cultures on human colonic smooth muscle and to explore their protective activity against LPS-induced myogenic morpho-functional alterations. METHODS: The effects of LGG (ATCC 53103 strain) and of supernatants have been tested on both human colonic smooth muscle strips and isolated cells in the absence or presence of LPS obtained from a pathogenic strain of Escherichia coli. Their effects on myogenic morpho-functional properties, on LPS-induced NFκB activation, and on cytokine production have been evaluated. Toll-like receptor 2 expression has been analyzed by qPCR and flow cytometry. KEY RESULTS: Lactobacillus rhamnosus GG exerted negligible transient effects per se whereas it was capable of activating an intrinsic myogenic response counteracting LPS-induced alterations. In particular, both LGG and supernatants significantly reduced the LPS-induced morpho-functional alterations of muscle cells, i.e. cell shortening and inhibition of contractile response. They also hindered LPS-induced pro-inflammatory effects by decreasing pro-inflammatory transcription factor NFκB activation and pro-inflammatory cytokine IL-6 secretion, and restored the secretion levels of anti-inflammatory cytokine IL10. CONCLUSIONS & INFERENCES: Taken together these data demonstrate that LGG protects human colonic smooth muscle from LPS-induced myogenic damage and might be beneficial on intestinal motor disorders due to bacterial infection.

Myogenic regional responsiveness to cholinergic and vipergic stimulation in human colon.

BACKGROUND: Differences in the actions of enteric neurotransmitters on colonic circular and longitudinal muscle layers have not been clearly determined, nor the possible existence of intrinsic myogenic phenotypes that might contribute to regional differences in human colon motor activity. The aim of this study was to analyze the direct pharmaco-mechanical coupling of carbachol (CCh) and vasoactive intestinal polypeptide (VIP) on human colonic smooth muscle strips and cells. METHODS: Circular and longitudinal muscle strips and cells were obtained from 15 human specimens of ascending and sigmoid colon. Both isometric tension on muscle strips and contraction and relaxation on cells were measured in response to increasing CCh and VIP concentrations. KEY RESULTS: Circular muscle strips of ascending colon were more sensitive to the effect of CCh than that of sigmoid colon, EC(50) values being, respectively, 4.15µmolL(-1) and 8.47µmolL(-1) (P<0.05), although there were no differences in maximal responses. No regional differences were observed in longitudinal muscle strips or in smooth muscle cells. Maximal responses to CCh were higher on circular than longitudinal muscle strips and cells throughout the colon. A greater sensitivity to VIP was observed in ascending colon compared with sigmoid colon, both in circular (EC(50:) 0.041 and 0.15µmolL(-1) , respectively, P<0.01) and longitudinal (EC(50:) 0.043 and 0.09µmolL(-1) , respectively, P<0.05) strips, and similar differences were observed in longitudinal smooth muscle cells (EC(50:) 44.85 and 75.24nmolL(-1) , respectively, P<0.05). CONCLUSIONS & INFERENCES: Regional myogenic differences in pharmaco-mechanical coupling between the enteric neurotransmitters and smooth muscle contribute to the complex regional motor patterns of human colon.