Disease relevance of Substance P

• CP-96,345, a specific non-peptide NK-1R antagonist, inhibited SP-induced rise of [Ca(2+)](i) in the astroglioma cells [1].
• Substance P (SP), a putative nociceptive transmitter, is increased in the CSF of patients with fibromyalgia syndrome (FMS) [2].
• 5. The results suggest (1) that ECT evokes ocular inflammation through antidromic C-fibre activation; (2) that SP contributes to the ECT-evoked miosis; and (3) that NO contributes to the antidromic C-fibre activation and possibly to the vascular responses mediated by the C-fibre transmitters [3].
• Inhibition by nociceptin of neurogenic inflammation and the release of SP and CGRP from sensory nerve terminals [4].
• 5. Capsaicin evoked SP release was increased in tissue taken from Crohn's disease but not ulcerative colitis patients [5].

High impact information on Substance P

• Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA [6].
• We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP [7].
• SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N omega-monomethyl-L-arginine [7].
• Because earlier observations indicated that only nociceptive dorsal horn neurons respond to substance P (SP), we examined which morphological types of lamina I neurons express receptors for SP (NK-1r) [8].
• Here, we report that in peripheral sensory neurons from embryonic chick dorsal root ganglia (DRG), the G protein-mediated inhibition of voltage-dependent calcium channels may best explain how norepinephrine (NE) and GABA inhibit the electrically evoked, calcium-dependent release of substance P (SP) [9].

Chemical compound and disease context of Substance P

• This study is aimed to investigate the relationship between plasma concentrations of nitrite and nitrate as a measure of ongoing nitric oxide (NO) production, the vasodilatory neuropeptides calcitonin gene-related peptide (CGRP) and substance P (SP), endotoxemia and hemodynamic changes in human septic shock [10].
• Serotonin (5-HT) and substance P (SP) were assayed in peripheral blood in patients with known midgut carcinoids and hepatic metastases [11].
• CONCLUSIONS: These results support the involvement of BKB1-R in the development of diabetic hyperalgesia in STZ-mice through activation of the NO, SP and CGRP pathways [12].

Biological context of Substance P

• ACh-, Bk-, and SP-elicited choroidal vasorelaxation was greater in saline-treated newborn than juvenile pigs [13].
• At the same dose, SP and NKA were more potent than [MePhe7]NKB in increasing MAP and HR, but did not produce water intake or wet dog shake behaviours [14].
• On the other hand, there was no noticeable change in gene expression and immunoreactivity of SP and CGRP [15].
• In contrast, SP, classic selective NK1 agonists, and antagonists had a high affinity for both types of binding sites [16].
• Substance P (SP) has been shown to stimulate the hydrolysis of inositol phospholipids in peripheral tissues and in the brain [17].

Anatomical context of Substance P

• Colocalization of NOS with VIP but not with SP was frequent in these nerve fibers [18].
• In epithelium, SP alone elicited a significant phosphoinositide breakdown, suggesting that epithelial receptors to tachykinins may be of the NK1 subtype [19].
• Thus, this study compared diameter responses to acetylcholine (ACH), bradykinin (BKN), and substance P (SP) between coronary microvessels (i.d.=106+/-4 microm) dissected from left ventricles of normotensive and hypertensive Dahl rats (Dahl-NT and Dahl-HT, respectively) [20].
• 2. Anatomical investigations were performed by injecting guinea-pig airways with the neuronal tracer Fast Blue. The animals were killed 7 days later, and the ganglia were removed and immunostained with antisera against substance P (SP) and neurofilament protein (NF) [21].
• SP-like immunoreactivity has been detected in nerve terminals innervating the adrenal medulla; however, little is known of the presence of other tachykinins in this tissue [22].

Associations of Substance P with other chemical compounds

• The results show that both NKA- and SP-like immunoreactivities are present in the adrenal medulla [22].
• Exposure to capsaicin produced simultaneous release of SP- and tachykinin-like immunoreactivity both in presence and absence of mucosa [23].
• Examination of consecutive sections immunostained for NT, enkephalin (Enk), GABA, and substance P (SP) revealed that 50% of neurons with NT-LI in the caudate nucleus and nucleus accumbens exhibited Enk-LI, 15% showed GABA-LI, and 5% manifested both Enk-LI and GABA-LI; no NT-positive neurons in the striatum and nucleus accumbens showed SP-LI [24].
• alpha-Bungarotoxin (alpha Bgt) was shown to inhibit the binding of the 125I-labeled substance P (SP) and eledoisin (EL) to the rat brain membranes with Kl values of 8.0 +/- 5.0 x 10(-8) and 1.1 +/- 0.5 x 10(-6) M, respectively [25].
• Short-term, stress-induced CA secretion is regulated biphasically by substance P (SP) which inhibits acetylcholine (ACh) action at SP greater than 10(-6) M and facilitates CA secretion in response to metabolic and physical stressors, ACh or electrical stimulation at SP less than 10(-6) M [26].
• The substance P receptor antagonist, CP-96,345, not only blocked AW- or PW-induced endogenous substance P expression but also abrogated AW- or PW-induced HIV replication in T cells [27].

Gene context of Substance P

• Beyond that, CGRP was able to boost sensitization, whereas SOM and SP did not show any effects on the sensitization process [28].
• TNFalpha attenuated SP- and NKA-induced relaxation in a time- and concentration-dependent manner, decreasing the ability of PGE(2) to relax tissues [29].
• Culture with PGE(2) decreased SP- and PGE(2)-mediated relaxation, further implicating the activity of COX-2 in the attenuation of tachykinin signalling [29].
• NK-1 receptor antagonists might be potent drugs for treatment of inflammatory liver disease, most likely by inhibiting SP effects [30].
• Thus, in adult rats, the C/SMG is as susceptible as the SCG to Gu treatment; the different pattern of hyperinnervation by SP, CGRP and VIP of the C/SMG as compared with the SCG may reflect the different sources for these neuropeptides in prevertebral as compared with paravertebral ganglia [31].
• We observed a time-dependent activation of ERK1/2, c-Jun N-terminal kinase (JNK), NFkappaB and activator protein-1 (AP-1) when pancreatic acini were stimulated with substance P [32].

Analytical, diagnostic and therapeutic context of Substance P

• NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA [7].
• The shift of the DRC for SP seen in response to vagotomy was only slightly reduced by capsaicin pretreatment [33].
• 4. Prevertebral ganglionectomy had no significant effect on the DRCs for SP and NKA, whereas vagotomy shifted the DRCs for all three test substances to the left [33].
• Adrenalectomy increased the content of VIP (35.4 +/- 4.0 (S.E.M.) vs control 11.9 +/- 1.1 pmol/g wet weight) but decreased that of SP (18.8 +/- 2.3 vs control 36.7 +/- 3.5 pmol/g wet weight) [34].
• Four weeks after transplantation, TH-immunoreactive fibers were distributed in the piloerector muscles, whereas SP- and CGRP-immunoreactive fibers were present around the hair follicles [35].

References