Roles for substance P and gastrin-releasing peptide as neurotransmitters released by primary afferent pruriceptors

Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of pruritogen-responsive DRG cells, 11.8–26.8%, 21.8–40.0%, and 21.4–26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.

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Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.2001.281.5.g1322 ◽

2001 ◽

Vol 281 (5) ◽

pp. G1322-G1328 ◽

Cited By ~ 54

Author(s):

Jaimie D. Nathan ◽

Akash A. Patel ◽

Douglas C. McVey ◽

Jean E. Thomas ◽

Veronica Prpic ◽

...

Keyword(s):

Substance P ◽

Sensory Neurons ◽

Serum Amylase ◽

Experimental Pancreatitis ◽

Vanilloid Receptor ◽

Primary Sensory Neurons ◽

P Release ◽

Vanilloid Receptor 1 ◽

Neurokinin 1 ◽

Substance P Release

We examined whether the capsaicin vanilloid receptor-1 (VR1) mediates substance P (SP) release from primary sensory neurons in experimental pancreatitis. Pancreatitis was achieved by 12 hourly injections of caerulein (50 μg/kg ip) in mice. One group received capsazepine (100 μmol/kg sc), a competitive VR1 antagonist, at 4-h intervals. Neurokinin-1 receptor (NK1R) internalization in acinar cells, used as an index of endogenous SP release, was assessed by immunocytochemical quantification of NK1R endocytosis. The severity of pancreatitis was assessed by measurements of serum amylase, pancreatic myeloperoxidase (MPO) activity, and histological grading. Caerulein administration caused significant elevations in serum amylase and pancreatic MPO activity, produced histological evidence of pancreatitis, and caused a dramatic increase in NK1R endocytosis. Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis. These results demonstrate that repeated caerulein stimulation causes experimental pancreatitis that is mediated in part by stimulation of VR1 on primary sensory neurons, resulting in endogenous SP release.

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Immunohistochemical localization of bombesin/gastrin-releasing peptide and substance P in primary sensory neurons

Journal of Neuroscience ◽

10.1523/jneurosci.03-10-02021.1983 ◽

1983 ◽

Vol 3 (10) ◽

pp. 2021-2029 ◽

Cited By ~ 123

Author(s):

P Panula ◽

M Hadjiconstantinou ◽

HY Yang ◽

E Costa

Keyword(s):

Substance P ◽

Sensory Neurons ◽

Immunohistochemical Localization ◽

Primary Sensory Neurons ◽

Gastrin Releasing Peptide

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Calcium and capsaicin- induced substance P release from peripheral terminals of primary sensory neurons

Regulatory Peptides ◽

10.1016/0167-0115(88)90337-0 ◽

1988 ◽

Vol 22 (1-2) ◽

pp. 117 ◽

Cited By ~ 14

Author(s):

C.A. Maggi ◽

P. Santicioli ◽

P. Geppetti ◽

R. Patacchini ◽

E. Del Bianco ◽

...

Keyword(s):

Substance P ◽

Sensory Neurons ◽

Primary Sensory Neurons ◽

P Release ◽

Substance P Release

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Capsaicin-evoked release of substance P from primary sensory neurons

Brain Research ◽

10.1016/0006-8993(79)90957-0 ◽

1979 ◽

Vol 170 (1) ◽

pp. 209-213 ◽

Cited By ~ 188

Author(s):

Elizabeth Theriault ◽

Masanori Otsuka ◽

Thomas Jessell

Keyword(s):

Substance P ◽

Sensory Neurons ◽

Primary Sensory Neurons

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THU0072 Gastrin-Releasing Peptide (GRP) and RC-3095, a GRP Receptor Antagonist, Regulates Arthritic Mice Synovial Fibroblasts

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.5209 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 218.1-218

Author(s):

V.S. Clarimundo ◽

M. Farinon ◽

C. Nör ◽

L.I. Filipin ◽

P.S. Gulko ◽

...

Keyword(s):

Receptor Antagonist ◽

Synovial Fibroblasts ◽

Gastrin Releasing Peptide ◽

Grp Receptor

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Sufentanil, Morphine, Met-enkephalin, and k-Agonist (U-50,488H) Inhibit Substance P Release from Primary Sensory Neurons

Anesthesiology ◽

10.1097/00000542-198904000-00022 ◽

1989 ◽

Vol 70 (4) ◽

pp. 672-677 ◽

Cited By ~ 48

Author(s):

H. Ming Chang ◽

Charles B. Berde ◽

George G. Holz ◽

Grieg F. Steward ◽

Richard M. Kream

Keyword(s):

Substance P ◽

Sensory Neurons ◽

Primary Sensory Neurons ◽

P Release ◽

Inhibit Substance ◽

Substance P Release

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Modulation of Substance P Release and Voltage-Dependent Ion Channels in Primary Sensory Neurons

Neurotransmitters, Receptors ◽

10.1016/b978-0-08-028022-6.50019-9 ◽

1982 ◽

pp. 155-166 ◽

Cited By ~ 1

Author(s):

T.M. Jessell ◽

G.D. Fischbach

Keyword(s):

Ion Channels ◽

Substance P ◽

Sensory Neurons ◽

Primary Sensory Neurons ◽

P Release ◽

Voltage Dependent ◽

Substance P Release

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Gastrin-releasing peptide directly releases pepsinogen from guinea pig chief cells

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1990.259.5.g760 ◽

1990 ◽

Vol 259 (5) ◽

pp. G760-G766 ◽

Cited By ~ 3

Author(s):

S. Fiorucci ◽

K. E. McArthur

Keyword(s):

Substance P ◽

Guinea Pig ◽

Receptor Antagonist ◽

Fold Increase ◽

Chief Cells ◽

Gastrin Releasing Peptide ◽

Basal Release ◽

Substance P Receptor ◽

Bombesin Receptor ◽

Muscarinic Agents

Gastrin-releasing peptide (GRP) and bombesin can stimulate pepsinogen release by both gastrin-dependent and -independent mechanisms. Using isolated guinea pig gastric chief cells, we determined that GRP can act directly on the guinea pig chief cell to cause pepsinogen release. GRP and bombesin stimulated a 2.5- to 3-fold increase in pepsinogen release above basal release. Substance P also stimulated a small but significant increase in pepsinogen release. No gastrin immunoreactivity was detected in the supernatants of cells stimulated with up to 1 microM GRP or bombesin or 1 mM carbachol. GRP-stimulated pepsinogen release was completely inhibited by GRP/bombesin receptor agonists as well as substance P receptor antagonist but not by antagonists to receptors for gastrin, the octapeptide of cholecystokinin (CCK-8), secretin, vasoactive intestinal peptide (VIP), or muscarinic agents. Substance P-stimulated pepsinogen release was completely inhibited by substance P receptor antagonist but not by GRP/bombesin receptor antagonists. An additive effect on pepsinogen release was seen when GRP was combined with maximally effective concentrations of adenosine 3',5'-cyclic monophosphate (cAMP)-mediated agents (VIP, secretin, 8-BrcAMP) but not with calcium-mediated agents (carbachol, CCK-8, gastrin). These results indicate that GRP can directly stimulate pepsinogen release from guinea pig chief cells by a specific GRP receptor that mobilizes intracellular calcium.

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