Expression of NK-1 and NK-3 tachykinin receptors in pancreatic acinar cells after acute experimental pancreatitis in rats.
Activation of neurokinin (NK)-1 receptors but not of NK-3 stimulates amylase release from isolated pancreatic acini of the rat. Immunofluorescence studies show that NK-1 receptors are more strongly expressed than NK-3 receptors on pancreatic acinar cells under basal conditions. No studies have examined the expression of the two NK receptor populations in pancreatic acini during pancreatitis in rats. We therefore investigated the relationships between expression of these two tachykinin receptors and experimental acute pancreatitis induced by stimulating pancreatic amylase with caerulein (CK) in rats. Hyperstimulation of the pancreas by CK caused an increase in plasma amylase and pancreatic water content and resulted in morphological evidence of cytoplasmic vacuolization. Immunofluorescence analysis revealed a similar percentage of NK-1 receptor antibody immunoreactive acinar cells in rats with pancreatitis and in normal rat tissue but a larger percentage of NK-3 receptor immunoreactive cells in acute pancreatitis than in normal pancreas. Western blot analysis of NK-1 and NK-3 receptor protein levels after CK-induced pancreatitis showed no change in NK-1 receptors but a stronger increase in NK-3 receptor expression in pancreatic acini compared with normal rats thus confirming the immunofluorescence data. These new findings support previous evidence that substance P-mediated functions within the pancreas go beyond sensory signal transduction contributing to neurogenic inflammation, and they suggest that substance P plays a role in regulating pancreatic exocrine secretion via acinar NK-1 receptors. The significant increase in NK-3 receptors during pancreatic stimulation suggests that NK-3 receptors also intervene in the pathogenesis of mild acute pancreatitis in rats.
Broccardo
Maria
M
Dipartimento di Fisiologia Umana e Farmacologia "V. Erspamer" Università di Roma "La Sapienza"- P.le A. Moro 5-00185 Roma, Italia.
Linari
Giorgio
G
Agostini
Simona
S
Amadoro
Giusi
G
Carpino
Francesco
F
Ciotti
Maria Teresa
MT
Petrella
Carla
C
Petrozza
Vincenzo
V
Severini
Cinzia
C
Improta
Giovanna
G
D000818:Animals; D002478:Cells, Cultured; D002108:Ceruletide; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D018042:Receptors, Neurokinin-3 / Q000378:metabolism*
D018040:Receptors, Neurokinin-1; D018042:Receptors, Neurokinin-3; D002108:Ceruletide