The Central Pharmacology of Primary Afferents with Emphasis on the Disposition and Role of Primary Afferent Substance P

1986 ◽  
pp. 165-195 ◽  
Author(s):  
Tony L. Yaksh
Keyword(s):  
Substance P ◽  
Primary Afferents ◽  
Primary Afferent

scholarly journals A9 DORSAL ROOT GANGLIA NEURONAL RESPONSES AND SUBSTANCE P PRODUCTION ARE HIGHER IN MALE MICE

2021 ◽  
Vol 4 (Supplement_1) ◽  
pp. 10-11
Author(s):  
J Pujo ◽  
G De Palma ◽  
J Lu ◽  
S M Collins ◽  
P Bercik
Keyword(s):  
Abdominal Pain ◽  
Substance P ◽  
Gut Microbiota ◽  
Sensory Neurons ◽  
Dorsal Root ◽  
Neuronal Response ◽  
Neuronal Responses ◽  
Visceral Sensitivity ◽  
Germ Free

Abstract Background Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to display visceral hypersensitivity, which normalizes after colonization. Sex also appears to play a key role in visceral sensitivity, as women report more abdominal pain than men. Thus, both gut bacteria and sex are important in the regulation of gut nociception, but the underlying mechanisms remain poorly understood. Aims To investigate the role of gut microbiota and sex in abdominal pain. Methods We used primary cultures of sensory neurons from dorsal root ganglia (DRG) of female and male conventionally raised (SPF) or germ-free (GF) mice (7–18 weeks old). To study the visceral afferent activity in vitro, calcium mobilization in DRG sensory neurons was measured by inverted fluorescence microscope using a fluorescent calcium probe Fluo-4 (1mM). Two parameters were considered i) the percentage of responding neurons ii) the intensity of the neuronal response. First, DRG sensory neurons were stimulated by a TRPV1 agonist capsaicin (12.5nM, 125nM and 1.25µM) or by a mixture of G-protein coupled receptors agonist (GPCR: bradykinin, histamine and serotonin; 1µM, 10µM and 100µM). We next measured the neuronal production of substance P and calcitonin gene-related peptide (CGRP), two neuropeptides associated with nociception, in response to capsaicin (1.25µM) or GPCR agonists (100µM) by ELISA and EIA, respectively. Results The percentage of neurons responding to capsaicin and GPCR agonists was similar in male and female SPF and GF mice. However, the intensity of the neuronal response was higher in SPF male compared to SPF female in response to capsaicin (125nM: p=0.0336; 1.25µM: p=0.033) but not to GPCR agonists. Neuronal activation was similar in GF and SPF mice of both sexes after administration of capsaicin or GPCR agonists. Furthermore, substance P and CGRP production by sensory neurons induced by capsaicin or GPCR agonists was similar in SPF and GF mice, regardless of sex. However, while the response to capsaicin was similar, the GPCR agonists-induced production of substance P was higher in SPF male mice compared to SPF females (p=0.003). The GPCR agonists-induced production of CGRP was similar in SPF male and female mice. Conclusions Our data suggest that at the level of DRG neurons, the absence of gut microbiota does not predispose to visceral hypersensitivity. The intensity of DRG neuronal responses to capsaicin and the GPCR agonists-induced production of substance P are higher in male compared to female mice, in contrast to previously published studies in various models of acute and chronic pain. Further studies are thus needed to investigate the role of sex in visceral sensitivity. Funding Agencies CIHR

Role of the C Domain of IGFs in Synergistic Promotion, with a Substance P–Derived Peptide, of Rabbit Corneal Epithelial Wound Healing

2004 ◽  
Vol 45 (4) ◽  
pp. 1125 ◽  
Author(s):  
Naoyuki Yamada ◽  
Ryoji Yanai ◽  
Masatsugu Nakamura ◽  
Makoto Inui ◽  
Teruo Nishida
Keyword(s):  
Wound Healing ◽  
Substance P ◽  
Corneal Epithelial ◽  
Epithelial Wound Healing

Role of substance P in allergic nasal symptoms in rats

2006 ◽  
Vol 532 (1-2) ◽  
pp. 155-161 ◽  
Author(s):  
Md. Ashequr Rahman ◽  
Toshio Inoue ◽  
Chiaki Kamei
Keyword(s):  
Substance P ◽  
Nasal Symptoms

Paradoxical effect of salbutamol in a model of acute organophosphates intoxication in guinea pigs: role of substance P release

2007 ◽  
Vol 292 (4) ◽  
pp. L915-L923 ◽  
Author(s):  
Jaime Chávez ◽  
Patricia Segura ◽  
Mario H. Vargas ◽  
José Luis Arreola ◽  
Edgar Flores-Soto ◽  
...  
Keyword(s):  
Substance P ◽  
Guinea Pigs ◽  
Smooth Muscle Contraction ◽  
In Vivo Experiments ◽  
Intracellular Ca ◽  
Neurokinin 1 ◽  
Substance P Release

Organophosphates induce bronchoobstruction in guinea pigs, and salbutamol only transiently reverses this effect, suggesting that it triggers additional obstructive mechanisms. To further explore this phenomenon, in vivo (barometric plethysmography) and in vitro (organ baths, including ACh and substance P concentration measurement by HPLC and immunoassay, respectively; intracellular Ca2+ measurement in single myocytes) experiments were performed. In in vivo experiments, parathion caused a progressive bronchoobstruction until a plateau was reached. Administration of salbutamol during this plateau decreased bronchoobstruction up to 22% in the first 5 min, but thereafter airway obstruction rose again as to reach the same intensity as before salbutamol. Aminophylline caused a sustained decrement (71%) of the parathion-induced bronchoobstruction. In in vitro studies, paraoxon produced a sustained contraction of tracheal rings, which was fully blocked by atropine but not by TTX, ω-conotoxin (CTX), or epithelium removal. During the paraoxon-induced contraction, salbutamol caused a temporary relaxation of ∼50%, followed by a partial recontraction. This paradoxical recontraction was avoided by the M2- or neurokinin-1 (NK1)-receptor antagonists (methoctramine or AF-DX 116, and L-732138, respectively), accompanied by a long-lasting relaxation. Forskolin caused full relaxation of the paraoxon response. Substance P and, to a lesser extent, ACh released from tracheal rings during 60-min incubation with paraoxon or physostigmine, respectively, were significantly increased when salbutamol was administered in the second half of this period. In myocytes, paraoxon did not produce any change in the intracellular Ca2+ basal levels. Our results suggested that: 1) organophosphates caused smooth muscle contraction by accumulation of ACh released through a TTX- and CTX-resistant mechanism; 2) during such contraction, salbutamol relaxation is functionally antagonized by the stimulation of M2 receptors; and 3) after this transient salbutamol-induced relaxation, a paradoxical contraction ensues due to the subsequent release of substance P.

The role of substance P in the pathogenesis of experimental allergic neuritis

1993 ◽  
Vol 46 (1-2) ◽  
pp. 251-253
Author(s):  
Shujian Wu ◽  
Juan Chen ◽  
Chengtao Xu
Keyword(s):  
Substance P ◽  
Experimental Allergic Neuritis ◽  
Experimental Allergic ◽  
Allergic Neuritis

scholarly journals The role of substance P as a neurotransmitter in the reflexes of slow time courses in the neonatal rat spinal cord

1985 ◽  
Vol 84 (3) ◽  
pp. 663-673 ◽  
Author(s):  
Hiroyuki Akagi ◽  
Shiro Konishi ◽  
Masanori Otsuka ◽  
Mitsuhiko Yanagisawa
Keyword(s):  
Spinal Cord ◽  
Substance P ◽  
Neonatal Rat ◽  
Rat Spinal Cord ◽  
Slow Time ◽  
Time Courses

Synthesis of a Substance P Antagonist with a Somatostatin Scaffold:  Factors Affecting Agonism/Antagonism at GPCRs and the Role of Pseudosymmetry

2000 ◽  
Vol 43 (21) ◽  
pp. 3827-3831 ◽  
Author(s):  
Josephine Liu ◽  
Dennis J. Underwood ◽  
Margaret A. Cascieri ◽  
Susan P. Rohrer ◽  
Louis-David Cantin ◽  
...  
Keyword(s):  
Substance P ◽  
Factors Affecting ◽  
Substance P Antagonist

Excitability of primary afferents in feline spinal cord: taurine, homotaurine, and γ-aminobutyric acid compared

1982 ◽  
Vol 60 (6) ◽  
pp. 850-855 ◽  
Author(s):  
Radan Čapek ◽  
Barbara Esplin
Keyword(s):  
Primary Afferents ◽  
Aminobutyric Acid ◽  
Primary Afferent Depolarization ◽  
Conditioning Stimulation ◽  
Primary Afferent ◽  
Antagonistic Muscle ◽  
Consistent Change ◽  
Muscle Nerve ◽  
Gaba Synthesis ◽  
Stimulation Of

Effects of taurine and homotaurine (3-aminopropancsuIfonic acid), on excitability of primary afferents were compared with effects of γ-aminobutyric acid (GABA) in spinal unanaesthesized cats. Homotaurine and GABA, administered intravenously or topically, produced a marked increase in afferent excitability. Homotaurine was about 10 times more potent than GABA. Taurine (up to 2 mmol/kg i.v., or 10 mM topically) did not produce a consistent change in afferent excitability. The effect of homotaurine was antagonized by bicuculline or picrotoxin in doses which suppressed the primary afferent depolarization, as indicated by an increase of afferent excitability, evoked by conditioning stimulation of an antagonistic muscle nerve. Semicarbazidc, an inhibitor of GABA synthesis, did not attenuate the homotaurine-induced excitability changes of afferents while suppressing entirely the primary afferent depolarization. These findings suggest that homotaurine exerts a direct GABA-like action on feline primary afferents.

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