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Distension-evoked reflex of rectorectal (R-R) contractions and rectointernal anal sphincter (R-IAS) relaxations can be generated in guinea pigs through an extrinsic sacral excitatory neural pathway (pelvic nerves) as well as intrinsic cholinergic excitatory and nitrergic inhibitory pathways. The aim of the present study was to create intrinsic R-R and R-IAS reflex models by pithing (destruction of the lumbar and sacral cords; PITH) and to evaluate whether the prokinetic benzamide mosapride, a 5-[HT.sub.4] receptor agonist, enhances these reflexes. The mechanical activities of the R-R and R-IAS were recorded in the anesthetized guinea pig on days 2-9 after PITH. Although the basal rectal pressure at distension after PITH was significantly lower than control, the reflex indexes of R-R contractions and synchronous R-IAS relaxations were unchanged between days 4 and 9 after PITH. The frequency of spontaneous rectal and IAS motility were also unchanged. Immunohistochemical studies revealed that the distribution of myenteric and intramuscular interstitial cells of Cajal (ICC) were not altered after PITH. Mosapride (0.1-1.0 mg/kg iv) dose-dependently increased both intrinsic R-R (maximum: 1.82) and R-IAS reflex indexes (maximum: 2,76) from control (1.0) 6-9 days after PITH. The 5-[HT.sub.4] receptor antagonist, GR-113808 (1.0 mg/kg iv) decreased the R-R and R-IAS reflex indexes by ~50% and antagonized the effect of mosapride (1.0 mg/kg iv). The present results indicate that mosapride moderately enhanced intrinsic R-R and R-IAS reflexes functionally compensated after deprivation of extrinsic nerves, mediated through endogenously active intrinsic 5-[HT.sub.4] receptors. extrinsic reflex; internal anal sphincter; intrinsic reflex; rectum

Abstract Prokineticin 2 (PK2) is a putative output molecule from the SCN. PK2 RNAlevels are rhythmic in the mouse SCN, with high levels during the day, and PK2 administration suppresses [...]

Byline: Sonja Fruhwald (1), Eva Herk (1), Heinz F. Hammer (2), Peter Holzer (3), Helfried Metzler (1) Keywords: Cerulein; Guinea pig; Intestinal motility; Neostigmine; Peristalsis; Prokinetic effect. Abstract: Objective: Cerulein and neostigmine are prokinetic drugs whose potency and effective dose range are barely known. The aim of this study was to assess their benefit for normal and compromised peristalsis. Design: In vitro, isolated segments of guinea pig small intestine. Setting : University laboratory. Interventions: Small bowel segments were mounted in tissue baths and luminally perfused with Tyrode solution. Test drugs (prokinetic: cerulein, neostigmine inhibitory: atropine, hexamethonium, epinephrine, sufentanil) were added to the tissue bath. Measurements and results: Peristalsis was quantified via changes in the peristaltic pressure threshold. One-way and two-way analysis of variance (ANOVA) were used for statistical analysis. Cerulein (0.03--100 nM) stimulated normal peristalsis in a concentration-dependent manner and reversed paralysis of peristalsis induced by all inhibitory test drugs to a similar extent. The properistaltic effect of neostigmine was limited to a narrow concentration range (0.03--0.1 AuM), whereas concentrations >0.3 AuM inhibited peristalsis. Neostigmine more effectively counteracted blockage of peristalsis caused by atropine than that caused by hexamethonium. The inhibitory effects of epinephrine and sufentanil on peristalsis were reversed only at the concentration range of 0.1--0.3 AuM neostigmine. Conclusions: Cerulein stimulates normal peristalsis in vitro at a wide concentration range and reverses blockage of peristalsis caused by drugs with a site of action either on the enteric nervous system or intestinal smooth muscle. Neostigmine's prokinetic effect, to the contrary, is limited to a small concentration range and best seen when peristalsis is depressed by blockage of cholinergic muscle activation. Author Affiliation: (1) Department of Anaesthesiology and Intensive Care Medicine, University of Graz, Auenbruggerplatz 29, 8036, Graz, Austria (2) Department of Internal Medicine, University of Graz, Graz, Austria (3) Department of Experimental and Clinical Pharmacology, University of Graz, Graz, Austria Article History: Registration Date: 01/04/2004 Received Date: 02/02/2004 Accepted Date: 30/03/2004 Online Date: 18/05/2004