Second Place — Resident Basic Science Award 1994: Subcellular Innervation Patterns of the Calcitonin Gene-Related Peptidergic Efferent Terminals in the Chinchilla Vestibular Periphery

1994 ◽  
Vol 111 (4) ◽  
pp. 385-395 ◽  
Author(s):  
Akira Ishiyama ◽  
Ivan Lopez ◽  
Phillip A. Wackym
Keyword(s):  
Vestibular System ◽  
Hair Cells ◽  
Calcitonin Gene Related Peptide ◽  
Type I ◽  
Type Ii ◽  
Primary Afferent ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Innervation Patterns ◽  
Immunoreactive Axons

We examined the ultrastructural distribution of calcitonin gene-related peptide immunoreactivity in the peripheral vestibular system of the chinchilla to study the Innervation patterns of this efferent neuropeptide. Immunoelectron microscopic localization of calcitonin gene-related peptide immunoreactive terminals in the maculae and cristae revealed an extensive innervation pattern on the afferent vestibular pathway. Calcitonin gene-related peptide immunoreactive terminals made synaptic contacts with the unmyelinated portions of the primary afferent vestibular dendrites innervating both type I and type II hair cells. Abundant synaptic contact between calcitonin gene-related peptide immunoreactive terminals and the chalices surrounding type I hair cells was observed. Direct contact between calcitonin gene-related peptide immunoreactive terminals and type II hair cells was observed. In addition, vesiculated efferent terminals without calcitonin gene-related peptide Immunoreactivity were seen synapsing on the chalices of type II hair cells and on the surrounding type I hair cells. The primary afferent somata in the vestibular ganglion of Scarpa did not contain calcitonin gene-related peptide Immunoreactivity. Unmyelinated calcitonin gene-related peptide immunoreactive axons passed among the primary afferent fibers in Scarpa's ganglion, and these fibers continued through the subepithelial regions of the vestibular end-organs. The calcitonin gene-related peptide immunoreactive axons ramified to produce numerous calcitonin gene-related peptide immunoreactive terminals throughout the neurosensory epithelium of the maculae and cristae. These data suggest that calcitonin gene-related peptide—mediated modulation of the afferent vestibular system is functionally important.

Calcitonin gene-related peptide containing primary afferent fibers synapse on primate spinothalamic tract cells

1990 ◽  
Vol 109 (1-2) ◽  
pp. 76-81 ◽  
Author(s):  
Susan M. Carlton ◽  
Karin N. Westlund ◽  
Dongxian Zhang ◽  
Linda S. Sorkin ◽  
William D. Willis
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Spinothalamic Tract ◽  
Primary Afferent ◽  
Related Peptide ◽  
Afferent Fibers ◽  
Calcitonin Gene ◽  
Primary Afferent Fibers

Plasticity of calcitonin gene related peptide neurotransmission in the spinal cord during peripheral inflammation

1995 ◽  
Vol 73 (7) ◽  
pp. 1007-1014 ◽  
Author(s):  
V. S. Seybold ◽  
M. T. Galeazza ◽  
M. G. Garry ◽  
K. M. Hargreaves
Keyword(s):  
Spinal Cord ◽  
Calcitonin Gene Related Peptide ◽  
Peripheral Inflammation ◽  
Afferent Neurons ◽  
Dorsal Spinal Cord ◽  
Primary Afferent Neurons ◽  
Primary Afferent ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Dorsal Spinal

Injection of complete Freund's adjuvant (CFA; 75 μL) into the plantar surface of the hind paw of the rat results in a mild inflammation that lasts for several days and is accompanied by hyperalgesia. Multiple components of calcitonin gene related peptide (CGRP) neurotransmission in the spinal cord are altered during the course of this peripheral inflammation. The content of immunoreactive (i) CGRP in the dorsal horn of the spinal cord, where primary afferent neurons terminate, is significantly decreased within 2 days after injection of CFA but increases to a level greater than that of the control at 8 days. The early decrease in iCGRP in the spinal cord suggests that the release of CGRP from primary afferent neurons is increased during the period of maximal hyperalgesia that accompanies peripheral inflammation. Changes in the mRNA for CGRP suggest that the increase in spinal content of iCGRP is due to an increase in synthesis of the peptide as the level of mRNA for CGRP is increased from 2 to 8 days after injection of CFA. Despite the decrease in the content of iCGRP in the spinal cord, there is no apparent decrease in the amount of iCGRP that can be released from the dorsal spinal cord by capsaicin; in fact, capsaicin-evoked release is increased at 4 days. Measurements of the binding of 125I-labelled CGRP in the dorsal spinal cord indicate that high affinity binding sites for CGRP are downregulated at 4 days after injection of CFA. In total, these data support the hypothesis that the activity of CGRP-containing primary afferent neurons is increased during peripheral inflammation. CGRP released from primary afferent neurons in the spinal cord may contribute to cellular changes that accompany peripheral inflammation.Key words: calcitonin gene related peptide, dorsal root ganglion, hyperalgesia, inflammation, spinal cord.

Angiotensin II mediates postischemic leukocyte-endothelial interactions: role of calcitonin gene-related peptide

2007 ◽  
Vol 292 (6) ◽  
pp. H3032-H3037 ◽  
Author(s):  
Mozow Yusof ◽  
Kazuhiro Kamada ◽  
F. Spencer Gaskin ◽  
Ronald J. Korthuis
Keyword(s):  
Angiotensin Ii ◽  
Nadph Oxidase ◽  
Calcitonin Gene Related Peptide ◽  
Type I ◽  
Receptor Blockade ◽  
Ang Ii ◽  
Cgrp Receptor ◽  
Related Peptide ◽  
Enhanced Production ◽  
Calcitonin Gene

Vascular inflammation and enhanced production of angiotensin II (ANG II) are involved in the pathogenesis of hypertension and diabetes, disease states that predispose the afflicted individuals to ischemic disorders. In light of these observations, we postulated that ANG II may play a role in promoting leukocyte rolling (LR) and adhesion (LA) in postcapillary venules after exposure of the small intestine to ischemia-reperfusion (I/R). Using an intravital microscopic approach in C57BL/6J mice, we showed that ANG II type I (AT1) or type II (AT2) receptor antagonism (with valsartan or PD-123319, respectively), inhibition of angiotensin-converting enzyme (ACE) with captopril, or calcitonin gene-related peptide (CGRP) receptor blockade (CGRP8-37) prevented postischemic LR but did not influence I/R-induced LA. However, both postischemic LR and LA were largely abolished by concomitant AT1 and AT2 receptor blockade or chymase inhibition (with Y-40079). Additionally, exogenously administered ANG II increased LR and LA, effects that were attenuated by pretreatment with a CGRP receptor antagonist or an NADPH oxidase inhibitor (apocynin). Our work suggests that ANG II, formed by the enzymatic activity of ACE and chymase, plays an important role in inducing postischemic LR and LA, effects that involve the engagement of both AT1 and AT2 receptors and may be mediated by CGRP and NADPH oxidase.

Calcitonin gene-related peptide inhibits interleukin-1β-induced endogenous monocyte chemoattractant protein-1 secretion in type II alveolar epithelial cells

2006 ◽  
Vol 291 (3) ◽  
pp. C456-C465 ◽  
Author(s):  
Wenjing Li ◽  
Tengke Wang ◽  
Chenming Ma ◽  
Tingting Xiong ◽  
Yi Zhu ◽  
...  
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Intracellular Camp ◽  
Type Ii ◽  
Monocyte Chemoattractant ◽  
Alveolar Epithelial ◽  
Monocyte Chemoattractant Protein ◽  
Related Peptide ◽  
Calcitonin Gene ◽  
Ros Formation ◽  
Proinflammatory Factor

As important multifunctional cells in the lung, alveolar epithelial type II (AEII) cells secrete numerous chemokines on various stimuli. Our previous data showed that AEII cells also express the neuropeptide calcitonin gene-related peptide (CGRP) and the proinflammatory factor interleukin (IL)-1β induces CGRP secretion in the A549 human AEII cell line. In the present study, the CGRP-1 receptor antagonist human (h)CGRP8–37(0.1–1 nM) greatly amplified the production of IL-1β-induced monocyte chemoattractant protein (MCP)-1. The inhibition of CGRP expression by small interfering RNA significantly increased MCP-1 secretion on IL-1β stimulation. However, exogenous hCGRP (10–100 nM) suppressed IL-1β-evoked MCP-1 secretion in MCP-1 promoter activity, and CGRP gene stably transfected cell clones significantly inhibited both the mRNA and protein levels of MCP-1 induced by IL-1β. These data imply that AEII-derived CGRP suppressed IL-1β-induced MCP-1 secretion in an autocrine/paracrine mode. Subsequent investigation revealed that CGRP inhibited IL-1β-evoked NF-κB activity by suppressing IκBα phosphorylation and degradation. Moreover, CGRP attenuated IL-1β-induced reactive oxygen species (ROS) formation, the early event in proinflammatory factor signaling. We previously showed that the CGRP inhibitory effect was mediated by elevated intracellular cAMP and show here that analogs of cAMP, 8-bromoadenosine 3′,5′-cyclic monophosphothioate and the Sp isomer of adenosine 3′,5′-cyclic monophosphothioate, mimicked the CGRP suppressive effect on IL-1β-induced ROS formation, NF-κB activation, and MCP-1 secretion. Thus increased endogenous CGRP secretion in lung inflammatory disease might eliminate the excessive response by elevating the cAMP level through inhibiting the ROS-NF-κB-MCP-1 pathway.

scholarly journals Structural studies on the [But-Cys18](19-37)-fragment of human β-calcitonin-gene-related peptide

1991 ◽  
Vol 280 (1) ◽  
pp. 147-150 ◽  
Author(s):  
J K Sagoo ◽  
C Bose ◽  
N R A Beeley ◽  
S J B Tendler
Keyword(s):  
Calcitonin Gene Related Peptide ◽  
Type I ◽  
Immune Recognition ◽  
Structural Studies ◽  
Structural Elements ◽  
Peptide Fragment ◽  
Beta Turn ◽  
Related Peptide ◽  
Calcitonin Gene

High-field n.m.r. studies were undertaken upon a peptide fragment of the C-terminal region of human beta-calcitonin-gene-related peptide (beta-hCGRP). Studies on the antigenic [Bu(t)-Cys18]beta-hCGRP-(19-37)-fragment revealed that several elements of secondary structure were present when the peptide was dissolved in [2H6]dimethyl sulphoxide. In particular an unspecified turn in the region of Ser19-Gly20 and a type I beta-turn in the region of Asn31-Val32-Gly33 were identified. Through-space connections between the terminal Phe37 amide group and the beta-protons of Thr50 suggest that the peptide may be folded into a loop-type conformation. These structural elements appear to overlap with the epitopes of a number of monoclonal antibodies and provide a molecular basis for understanding the role of the terminal Phe37 amide residue in the immune recognition of beta-hCGRP.

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