Transient Receptor Potential Vanilloid (TRPV-1) Promotes Neurogenic Inflammation in the Pancreas Via Activation of the Neurokinin-1 Receptor (NK-1R)

Abstract

Activation of TRPV-1 induces SP-mediated plasma extravasation in the rat pancreas via activation of the NK1-R. TRPV-1 mediates neurogenic inflammation in cerulein-induced pancreatitis in the rat.

Targeting Calcium Channels to Block Tumor Vascularization

“…TRPV1 mediates neurogenic inflammation in pancreatitis, and the effect is blocked by pretreatment with TRPV1 antagonist capsazepine or NK1 receptor antagonist CP96, 345 [12,59]. Notably, an increase in plasma H2S levels is induced in caerulein-induced pancreatitis and the therapeutic administration of PAG attenuates the pancreatic inflammation and partially reverses the associated lung injury [56].…”

“…Furthermore, TRPA1 is sensitive to thiol-reactive electrophiles that bind to cysteine residues located in the NH2-terminus of the channel [55]. In addition, H2S and its donors trigger TRPV1 opening that mediates chloride secretion in colon, gut motility, acute pancreatitis, airway constriction, and bladder contractility [12,[56][57][58][59][60][61]. Serosal application of NaHS (0.2-2.5 mM) and L-cysteine stimulates luminal chloride secretion by guinea pig, rat and human colon [12,40,58].…”

Substance P (SP)

“…Primary sensory neurons that innervate the tissues contain an abundance of neurotransmitters, including substance P. Transient receptor potential vanilloid type 1 (TRPV1) channels located on these neurons, when activated, causes neuronal release of stored substance P. It was demonstrated in vivo that capsazepine, a TRPV1 antagonist, significantly reduced inflammation and pancreatic injury in caerulein-induced acute pancreatitis (47). On the other hand, activation of TRPV1 by capsaicin caused release of substance P, and exaggerated caerulein-induced acute pancreatitis (28). Pre-treatment of capsazepine or CP96,345 before administration of capsaicin showed reduced severity of acute pancreatitis, highlighting the importance of TRPV1 and NK1R (28).…”

“…On the other hand, activation of TRPV1 by capsaicin caused release of substance P, and exaggerated caerulein-induced acute pancreatitis (28). Pre-treatment of capsazepine or CP96,345 before administration of capsaicin showed reduced severity of acute pancreatitis, highlighting the importance of TRPV1 and NK1R (28). High doses of Resiniferatoxin caused disruption of the celiac ganglion and inhibited substance P release, and showed protective effects against caeruleininduced pancreatitis in rats (49).…”

“…Specific NK1R antagonists a) CP96,345 (Compound ID:104943). It has been used in several acute pancreatitis studies with success (28,38,41 (71). It was shown to stimulate pancreatic plasma extravasation via NK1R activation (21).…”