sincalide and Spasm

Recent developments of manometric and endoscopic instrumentation have rekindled interest in sphincter of Oddi function. As a result of human and animal studies, our understanding of normal sphincter of Oddi physiology has increased and possible motility abnormalities are being identified. Manometric studies have shown that the sphincter of Oddi is characterized by prominent phasic contractions which are super-imposed on a low tonic pressure. The phasic contractions are orientated mainly in an antegrade direction; however, both simultaneous and retrograde contractions are registered. Cineradiography has demonstrated that the phasic contractions have a propulsive function, expelling small volumes of fluid from the common bile duct into the duodenum. Intravenously administered cholecystokinin-octapeptide normally inhibits the phasic contractions and reduces the sphincter tone. Motility abnormalities may occur if the sphincter of Oddi exhibits abnormally high tone, alteration in the direction of the phasic contractions, abnormal changes in the contraction frequency, or abnormal responses to hormonal stimulation. Preliminary human studies demonstrate disorders in sphincter of Oddi motility patterns, suggesting that motility abnormalities may be associated with choledocholithiasis, dyskinesia and idiopathic relapsing pancreatitis.

Topics: Ampulla of Vater; Animals; Common Bile Duct Diseases; Duodenum; Humans; Manometry; Morphine; Movement; Muscle Contraction; Sincalide; Spasm; Sphincter of Oddi; Time Factors

The tachykinin NK1 receptor agonist substance P methyl ester (SPOME) impedes intestinal peristalsis by releasing nitric oxide (NO) from inhibitory motor neurones. Since NK1 receptor agonists differ in their receptor interaction, we set out to compare a range of NK1 receptor agonists including SPOME, septide and GR-73 632 in their effects on propulsive peristalsis and circular muscle activity in the guinea-pig isolated small intestine. SPOME (100-300 nM) inhibited peristalsis by a rise of the pressure threshold at which peristaltic waves were triggered, whereas septide and GR-73 632 (30-300 nM) interrupted peristalsis by causing circular muscle spasms. Separate experiments showed that all three NK1 receptor agonists caused contraction of the circular muscle, which was enhanced by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (300 mM) and the P2X purinoceptor antagonist suramin (300 mM). In contrast, tetrodotoxin (300 nM) augmented the contractile effect of septide and GR-73 632 but not that of SPOME. It is concluded that the motor response to NK1 receptor agonists involves release of NO and adenosine triphosphate from inhibitory motor neurones. However, the NK1 receptor agonists differ in the mechanism by which they cause inhibitory transmitter release, which corresponds to differences in their antiperistaltic action.

Topics: Adenosine Triphosphate; Animals; Enzyme Inhibitors; Female; Guinea Pigs; Intestine, Small; Male; Motor Neurons; Muscle Contraction; Muscle, Smooth; Neurokinin A; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Peptide Fragments; Peristalsis; Piperidines; Purinergic P2 Receptor Antagonists; Pyrrolidonecarboxylic Acid; Quinuclidines; Receptors, Neurokinin-1; Receptors, Neurokinin-2; Receptors, Neurokinin-3; Sincalide; Spasm; Substance P; Suramin; Tetrodotoxin

Sphincter of Oddi dysfunction has been implicated as a cause of various forms of acute pancreatitis. However, there is no direct evidence to show that sphincter of Oddi dysfunction can cause obstruction of trans-sphincteric flow resulting in acute pancreatitis.. To determine if induced sphincter of Oddi spasm can produce trans-sphincteric obstruction and, in combination with stimulated pancreatic secretion, induce acute pancreatitis.. In anaesthetised possums, the pancreatic duct was ligated and pancreatic exocrine secretion stimulated by cholecystokinin octapeptide/secretin to induce acute pancreatitis. In separate animals, carbachol was applied topically to the sphincter of Oddi to cause transient sphincter obstruction. Sphincter of Oddi motility, trans-sphincteric flow, pancreatic duct pressure, pancreatic exocrine secretion, plasma amylase levels, and pancreatic tissue damage (histology score) were studied and compared with variables in ligation models.. Acute pancreatitis developed following stimulation of pancreatic exocrine secretion with peptides after pancreatic duct ligation (p<0.05). Neither pancreatic duct ligation nor stimulation of pancreatic exocrine secretion with cholecystokinin octapeptide/secretin alone resulted in acute pancreatitis. Topical carbachol stimulated sphincter of Oddi motility abolished trans-sphincteric flow, and increased pancreatic exocrine secretion (p<0.05) and pancreatic duct pressure to levels comparable with pancreatic duct ligation (p<0.001). Carbachol application (with or without combined peptide stimulation) elevated plasma amylase levels (p<0.01) and produced pancreatic tissue damage (p<0.05). Decompression of pancreatic duct ameliorated these effects (p<0.05).. Induced sphincter of Oddi dysfunction when coupled with stimulated pancreatic secretion causes acute pancreatitis. This may be an important pathophysiological mechanism causing various forms of acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Carbachol; Female; Ligation; Male; Opossums; Pancreatitis; Sincalide; Spasm; Sphincter of Oddi