Nicotinic stimulation of splenic T cells is protective in endoscopic retrograde cholangiopancreatography-induced acute pancreatitis in mice.

Abstract

It has previously been shown that current smoking is protective against endoscopic retrograde cholangiopancreatography (ERCP)-induced acute pancreatitis, but the mechanism of this effect was not identified. We tested the hypothesis that nicotine is the active factor in this protection in a mouse model of ERCP. Pretreatment with nicotine dose dependently inhibited acute pancreatitis caused by infusion of ERCP contrast solution into the main pancreatic duct in mice. 3-2,4-Dimethoxybenzylidene anabaseine (GTS-21), a specific partial agonist of the α7 nicotinic cholinergic receptor (α7nAChR), also protected the pancreas against ERCP-induced acute pancreatitis. The effects of GTS-21 were abolished by pretreatment with the nicotinic receptor antagonist mecamylamine. Surgical splenectomy performed 7 days before ERCP-induced pancreatitis blocked the protective effects of GTS-21. Intravenous injection of a crude preparation of total splenocytes prepared from mice pretreated with GTS-21 inhibited ERCP-induced pancreatitis; splenocytes from mice treated with vehicle had no effect. When T cells were removed from the crude GTS-21-treated splenocyte preparation by immunomagnetic separation, the remaining non-T-cell splenocytes did not protect against ERCP-induced acute pancreatitis. We conclude that nicotine protects against ERCP-induced acute pancreatitis and that splenic T cells are required for this effect. Stimulation of α7 nicotinic cholinergic receptors may protect against ERCP-induced acute pancreatitis and may also be a novel approach to therapeutic reversal of ongoing acute pancreatitis.NEW & NOTEWORTHY Epidemiological evidence indicated that acute smoking reduced the risk of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis, but the mechanism has remained elusive. The current findings indicate the nicotine reduces the severity of ERCP-induced pancreatitis by stimulating a population of splenic T cells that exert a protective effect on the pancreas. These findings raise the possibility that nicotinic agonists might be useful in treating pancreatitis.

• Authors: Rafiq A Shahid, Steven R Vigna, Min-Nung Huang, Michael D Gunn, Rodger A Liddle
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 323 Issue 5 Pg. G420-G427 (11 01 2022) ISSN: 1522-1547 [Electronic] United States
• PMID: 36126221 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• 3-(2,4-dimethoxybenzylidene)anabaseine
• Nicotine
• Mecamylamine
• Nicotinic Agonists
• alpha7 Nicotinic Acetylcholine Receptor

Topics

• Mice
• Animals
• Cholangiopancreatography, Endoscopic Retrograde (adverse effects)
• Pancreatitis (etiology)
• Nicotine
• Mecamylamine
• Nicotinic Agonists (pharmacology)
• Acute Disease
• alpha7 Nicotinic Acetylcholine Receptor
• Spleen
• T-Lymphocytes