PMID- 20659297
OWN - NLM
STAT- MEDLINE
DCOM- 20110208
LR  - 20210223
IS  - 1365-2982 (Electronic)
IS  - 1350-1925 (Linking)
VI  - 22
IP  - 11
DP  - 2010 Nov
TI  - Cannabinoid agonist WIN55,212 in vitro inhibits interleukin-6 (IL-6) and monocyte 
      chemo-attractant protein-1 (MCP-1) release by rat pancreatic acini and in vivo 
      induces dual effects on the course of acute pancreatitis.
PG  - 1248-56, e323
LID - 10.1111/j.1365-2982.2010.01569.x [doi]
AB  - BACKGROUND: Cannabinoids (CBs) evoke their effects by activating the cannabinoid 
      receptor subtypes CB1-r and CB2-r and exert anti-inflammatory effects altering 
      chemokine and cytokine expression. Various cytokines and chemokines are produced 
      and released by rodent pancreatic acini in acute pancreatitis. Although CB1-r and 
      CB2-r expressed in rat exocrine pancreatic acinar cells do not modulate digestive 
      enzyme release, whether they modulate inflammatory mediators remains unclear. We 
      investigated the CB-r system role on exocrine pancreas in unstimulated conditions 
      and during acute pancreatitis. METHODS: We evaluated in vitro and in vivo changes 
      induced by WIN55,212 on the inflammatory variables amylasemia, pancreatic edema 
      and morphology, and on acinar release and content of the cytokine interleukin-6 
      (IL-6) and chemokine monocyte chemo-attractant protein-1 (MCP-1) in untreated 
      rats and rats with caerulein (CK)-induced pancreatitis. KEY RESULTS: In the in 
      vitro experiments, WIN55,212 (10(-6) mol L(-1)) inhibited IL-6 and MCP-1 release 
      from acinar cells of unstimulated rats and after CK-induced pancreatitis. In 
      vivo, when rats were pretreated with WIN55,212 (2 mg kg(-1), intraperitoneally) 
      before experimentally-induced pancreatitis, serum amylase, pancreatic edema and 
      IL-6 and MCP-1 acinar content diminished and pancreatic morphology improved. 
      Conversely, when rats with experimentally-induced pancreatitis were post-treated 
      with WIN55,212, pancreatitis worsened. CONCLUSIONS & INFERENCES: These findings 
      provide new evidence showing that the pancreatic CB1-r/CB2-r system modulates 
      pro-inflammatory factor levels in rat exocrine pancreatic acinar cells. The dual, 
      time-dependent WIN55,212-induced changes in the development and course of acute 
      pancreatitis support the idea that the role of the endogenous CB receptor system 
      differs according to the local inflammatory status.
CI  - (c) 2010 Blackwell Publishing Ltd.
FAU - Petrella, C
AU  - Petrella C
AD  - Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, 
      Italy.
FAU - Agostini, S
AU  - Agostini S
FAU - Alema', G S
AU  - Alema' GS
FAU - Casolini, P
AU  - Casolini P
FAU - Carpino, F
AU  - Carpino F
FAU - Giuli, C
AU  - Giuli C
FAU - Improta, G
AU  - Improta G
FAU - Linari, G
AU  - Linari G
FAU - Petrozza, V
AU  - Petrozza V
FAU - Broccardo, M
AU  - Broccardo M
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neurogastroenterol Motil
JT  - Neurogastroenterology and motility
JID - 9432572
RN  - 0 (Benzoxazines)
RN  - 0 (Cannabinoids)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Gastrointestinal Agents)
RN  - 0 (Interleukin-6)
RN  - 0 (Morpholines)
RN  - 0 (Naphthalenes)
RN  - 0 (Quinolines)
RN  - 5H31GI9502 
      ((3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone)
RN  - 888Y08971B (Ceruletide)
RN  - CX56TX9Y1I (bicinchoninic acid)
RN  - EC 3.2.1.- (Amylases)
SB  - IM
MH  - Amylases/blood
MH  - Animals
MH  - Benzoxazines/*pharmacology
MH  - Body Water/metabolism
MH  - Cannabinoids/*agonists
MH  - Ceruletide
MH  - Chemokine CCL2/*antagonists & inhibitors/metabolism
MH  - Edema/pathology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Gastrointestinal Agents
MH  - Interleukin-6/*antagonists & inhibitors/metabolism
MH  - Male
MH  - Morpholines/*pharmacology
MH  - Naphthalenes/*pharmacology
MH  - Pancreas/drug effects/*metabolism/pathology
MH  - Pancreatitis/chemically induced/*drug therapy/pathology
MH  - Quinolines/metabolism
MH  - Rats
EDAT- 2010/07/28 06:00
MHDA- 2011/02/09 06:00
CRDT- 2010/07/28 06:00
PHST- 2010/07/28 06:00 [entrez]
PHST- 2010/07/28 06:00 [pubmed]
PHST- 2011/02/09 06:00 [medline]
AID - NMO1569 [pii]
AID - 10.1111/j.1365-2982.2010.01569.x [doi]
PST - ppublish
SO  - Neurogastroenterol Motil. 2010 Nov;22(11):1248-56, e323. doi: 
      10.1111/j.1365-2982.2010.01569.x.