Characteristics of the premature phase 3 of the migrating motor complex evoked by pirenzepine administration in the small bowel of non-fasted sheep
More details
Hide details
Department of Biostructure and Animal Physiology, Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Wrocław, Poland
Krzysztof Romański   

Department of Biostructure and Animal Physiology, Faculty of Veterinary Medicine, University of Environmental and Life Sciences, Norwida 31, 50-375 Wrocław, Poland.
J Pre Clin Clin Res. 2010;4(1):47–51
In sheep, pirenzepine (Pi) blocks muscarinic receptors thus inhibiting the gastrointestinal motility. However, its small doses also evoke the premature phase 3 of the migrating motor complex (MMC). The aim of this study was to specify further the character of stimulatory alterations caused by the drug in non-fasted sheep. The experiments were carried out in four conscious rams with sewn duodenal strain gauge force transducer and duodeno-jejunal bipolar electrodes. Following the control period, 0.15 M NaCl or Pi, at the dose 0.02 mg/kg body weight, were slowly administered into the jugular vein and motor-myoelectric activity recordings were continued until normal motility returned. In the course of most experiments Pi evoked the premature phase 3 preceded by 3-5 min inhibition in non-fasted rams. Its duration in the duodenum was shorter than in the jejunum and the same difference was observed in normal phase 3 of the MMC. Amplitude and duration of the spike bursts forming the premature phase 3 was not significantly different from normal phase 3 of the MMC cycle. The premature phase 3 exhibited a regularly propagating character in most cases, but occurred also in incomplete or disorganized forms. Usually, its character thus closely resembled the normal phase 3 of the MMC. It appears that Pi, at the low doses, triggers the premature phase 3 via the blockade of neuronal M1 receptor subtype that provokes the secondary activation of acetylcholine release. Induction of premature phase 3 by a small dose of Pi resembles the effect observed in monogastric species.
Code CF, Marlett JA: The interdigestive myo-electric complex of the stomach and small bowel of dogs. J Physiol (Lond) 1975, 246, 289- 309.
Sarna SK: Cyclic motor activity; migrating motor complex: 1985. Gastroenterology 1985, 89, 894-913.
El-Sharkawy TY, Markus H, Diamant NE: Neural control of the intestinal migrating myoelectric complex. A pharmacological analysis. Can J Physiol Pharmacol 1982, 60, 794-804.
Ormsbee III HS, Telford GL, Mason GR: Required neural involvement in control of canine migrating motor complex. Am J Physiol 1979, 237, E451-E456.
Burks TF: Actions of drugs on gastrointestinal motility. In: L R Johnason (Ed.): Physiology of the Gastrointestinal Tract, Raven Press, New York 1981, 495-516.
Daniel EE: Pharmacology of adrenergic, cholinergic, and drugs acting on other receptors in gastrointestinal muscle. In: G Bertaccini (Ed.):.
Handbook of Experimental Pharmacology, Springer-Verlag, Berlin 1982, 249-322.
Hammer R, Berrie CP, Birdsall NJM, Burgen ASV, Hulme EC: Pirenzepine distinguishes between diff erent subclasses of muscarinic receptors. Nature 1980, 283, 90-92.
Caulfi eld MP, Birdsall NJM: International Union of Pharmacology. XVII. Classifi cation of muscarinic acetylcholine receptors. Pharmacol Rev 1999, 50, 279-290.
Eglen RM, Hedge SS, Watson N: Muscarinic receptor subtypes and smooth muscle function. Pharmacol Rev 1996, 48, 531-565.
Dobrilla G, De Pretis G, Comberlato M, Amplatz S: Pirenzepine and upper gastrointestinal tract motility in man. Hepato-gastroenterol 1988, 35, 51-53. 11. Fox JET, Daniel EE., Jury J, Robotham H: Muscarinic inhibition of canine small intestinal motility in vivo. Am J Physiol 1985, 248, G526- G531.
Schworer H, Kilbinger H: Enhancement of guinea-pig intestinal peristalsis by blockade of muscarinic M1-receptors. Br J Pharmacol 1988, 93, 715-720.
Kleibeuker JH, Jansen JBMJ, Lamers CBHW: Cholinergic regulation of PP release is mediated through muscarinic M1-receptors. Digestion 1989, 43, 60-65.
Romański KW: Antral myoelectric activity in sheep: the eff ect of feeding and anticholinergic drug administration during various phases of migrating myoelectric complex. Acta Vet Beograd 2002, 52, 235-248.
Romański KW: Characterictisc and cholinergic control of the ‘minute rhythm’ in ovine antrum, small bowel and gallbladder. J Vet Med A 2002, 49, 313-320.
Romański KW: Character and cholinergic control of myoelectric activity in ovine duodenal bulb: relationships to adjacent regions. Vet Arhiv 2003, 73, 1-16.
Romański KW: The rebound excitation triggered by anticholinergic drugs from ovine pyloric antrum, small bowel and gallbladder. J Physiol Pharmacol 2003, 54, 121-133.
Romański KW: The role of muscarinic and nicotinic receptors in the control of the ovine pyloric antral myoelectric response to nutrients during individual phases of the migrating myoelectric complex. Small Rumin Res 2005, 57, 121-131.
Romański KW, Sławuta P: Role of cholinergic receptor subtypes upon the antro-duodenal coordination in sheep. J Physiol Pharmacol 2001, 52, suppl. II, 47 (abstr).
Romański KW, Sławuta P: Cholinergic control of pacemaker initiating phase III of the migrating myoelectric complex in sheep. J Anim Feed Sci 2002, 11, 637-650.
Sue R, Toomey ML, Todisco A, Soll AH, Yamada T: Pirenzepinesensitive muscarinic receptors regulate gastric somatostatin and gastrin. Am J Physiol 1985, 248, G184-G187.
Zaccaria M, Giordano G, Pasquali C, Ragazzi E, Zeviani M, Valentini P, Scandellari C: Eff ects of pirenzepine on plasma insulin, glucagon and pancreatic polypeptide levels in normal man. Eur J Clin Pharmacol 1985, 27, 701-705.
Romański KW, Goździewska K: Specifi c eff ect of pirenzepine on myoelectric and motor activity in ovine small bowel. Rev Med Vet 2010, 161, 401-408.
Romański KW: The importance of refractoriness in ovine antral digestive and interdigestive motility. Turk J Vet Anim Sci 2006, 30, 1-6.
Snedecor WG, Cochran GW: Statistical Methods (6th edn.), Iowa State University Press, Ames 1971.
Schiavone A, Sagrada A, Pagani F, Giachetti A: Role of muscarinic receptor subtypes in the regulation of migrating myoelectric complex in the dog. Gastroenterology 1989, 96, 116-121.
De Ponti F, Einaudi A, Cocentino M, D’Angelo L, Lecchini S., Frigo GM, Crema A: Diff erential eff ects of antimuscarinic agents on intestinal motility in the conscious dog. J Pharmacol Exp Ther 1993, 264, 789- 794.
Nelson DK, Pieramico O, Dahmen G, Dominguez-Munoz JE, Malfertheiner P, Adler G: M1-muscarinic mechanisms regulate interdigestive cycling of motor and secretory activity in human upper gut. Dig Dis Sci 1996, 41, 2006-2015.
Olgart C, Iversen HH: Nitric oxide-dependent relaxation induced by M1 muscarinic receptor activation in the rat small intestine. Br J Pharmacol 1999, 127, 309-313.
Daeffl er L, Schmidlin F, Gies J-P, Landry Y: Inverse agonist activity of pirenzepine at M2 muscarinic acetylcholine receptors. Br J Pharmacol 1999, 126, 1246-1252.
Mitsui M, Karaki H: Dual eff ects of carbachol on cytosolic Ca2+ and contraction in intestinal smooth muscle. Am J Physiol 1990, 258, C787-C793.
Ehlert FJ: Contractile role of M2 and M3 muscarinic receptors in gastrointestinal, airway and urinary bladder smooth muscle. Life Sci 2003, 74, 355-366.
Okamoto H, Prestwich SA, Asai S, Unno T, Bolton TB, Komori S: Muscarinic agonist potencies at three diff erent eff ector systems linked to the M2 or M3 receptor in longitudinal smooth muscle of guinea-pig small intestine. Br J Pharmacol 2002, 135, 1765-1775.
Ehlert FJ, Ostrom RS, Sawyer GW: Subtypes of the muscarinic receptor in smooth muscle. Life Sci 1997, 61, 1729-1740.
Micheletti R, Schiavone A, Giachetti A: Inhibitory muscarinic receptors involved in gastrointestinal motility. Prog Pharmacol Clin Pharmacol 1989, 7/1, 75-82.
Ogishima M, Kaibara M, Ueki S, Kurimoto T, Taniyama K: Z-338 facilitates acetylcholine release from enteric neurons due to blockade of muscarinic autoreceptors in guinea pig stomach. J Pharmacol Exp Ther 2000, 294, 33-37.
Sarna SK: Molecular, functional, and pharmacological targets for the development of gut promotility drugs. Am J Physiol 2006, 291, G545-G555.
Stengel PW, Cohen ML: M1 receptor-mediated nitric oxide-dependent relaxation unmasked in stomach fundus from M3 receptor knockout mice. J Pharmacol Exp Ther 2003, 304, 675-682.
Wallis RM, Napier CM: Muscarinic antagonists in development for disorders of smooth muscle function. Life Sci 1999, 64, 396-401.
Coulson FR, Jacoby DB, Fryer AD: Increased function of inhibitory neuronal M2 muscarinic receptors in trachea and ileum of diabetic rats. Br J Pharmacl 2002, 135, 1355-1362.
Harrington AM, Hutson JM, Southwell BR: Immunohistochemical localisation of pre-synaptic muscarinic receptor subtype-2 (M2r) in the enteric nervous system of guinea-pig ileum. Cell Tissue Res 2008, 332, 37-48.
Hammer R, Giraldo E, Giachetti A: Pirenzepine, the fi rst M1 receptor antagonist. In: Receptor Update. With special reference to pirenzepine, a selective muscarinic blocking Drug, Asia Pacifi c Congress Series No Excerpta Medica, Sydney 1982, 90-101.
Coulie B, Tack J, Peeters T, Janssens J: Involvement of two diff erent pathways in the motor eff ects of erythromycin on the gastric antrum in humans. Gut 1998, 43, 395-400.
Brown EN, Galligan JJ: Muscarinic receptors couple to modulation of nicotinic ACh receptor desensitization in myenteric neurons. Am J Physiol 2003, 285, G37-G44.
Mandl P, Kiss JP: Role of presynaptic nicotinic acetylcholine receptors in the regulation of gastrointestinal motility. Brain Res Bull 2007, 72, 194-200.
Gregory PC, Rayner DV, Wenham G: Initiation of migrating myoelectric complex in sheep by duodenal acidifi cation and hyperosmolarity. J Physiol (Lond) 1984, 355, 509-521.
Englander EW, Greeley Jr GH: Postpyloric gastrointestinal peptides 2006. In: L R Johnson (Ed.): Physiology of the Gastrointestinal Tract, Elsevier, Amsterdam 2006, 121-159.
Goyal RK: Identifi cation, localization and classifi cation of muscarinic receptor subtypes in the gut. Life Sci 1988, 43, 2209-2220.
Ruckebusch Y: Gastrointestinal motor functions in ruminants. In: S G Schultz (Ed.): Handbook of Physiology. The Gastrointestinal System, American Physiological Society, Bethesda 1989, 1225-1282.