Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)

Chiba, Tsutomu; Yamaguchi, Akinori; Yamatani, Toshiyuki; Nakamura, Akira; Morishita, Takahiro; Inui, Tetsuya; Fukase, Masaaki; Noda, Toshiharu; Fujita, Takashi

doi:10.1152/ajpendo.1989.256.2.e331

Cited by 211 publications

(188 citation statements)

References 15 publications

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“…Further in vivo experiments are needed to define the effects of inhibition of CGRP release from sensory nerves on insulin-mediated glucose metabolism, utilizing specific CGRP receptor antagonists [35] and capsaicin receptor antagonists [5]. The use of such antagonists and neonatal capsaicin treatment will help to define more clearly the role of CGRP and other neuropeptides in animal models of insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

1998

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Section: Discussionmentioning

confidence: 99%

Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

1998

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“…It was recently suggested that CGRP-R antagonists could be effective in treating migraine (19). To address this issue, we used three selective CGRP-R antagonists: MK-8825, a new and selective CGRP antagonist with a good oral bioavailability in rodents (25); BIBN4096BS (olcegepant), a high-affinity antagonist with established clinical efficacy in migraine (26-28); and CGRP 8-37, the first peptidic CGRP fragment used as a CGRP-R antagonist (29,30). We first induced a CSD episode in the control condition by bath application of 26 mM KCl.…”

Section: High Potassium Concentration Evokes Reproducible Csd In Rat mentioning

confidence: 99%

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Tozzi

Iure

Filippo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

123

117

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Cortical spreading depression (CSD) is a key pathogenetic step in migraine with aura. Dysfunctions of voltage-dependent and receptor-operated channels have been implicated in the generation of CSD and in the pathophysiology of migraine. Although a known correlation exists between migraine and release of the calcitonin gene-related peptide (CGRP), the possibility that CGRP is involved in CSD has not been examined in detail. We analyzed the pharmacological mechanisms underlying CSD and investigated the possibility that endogenous CGRP contributes to this phenomenon. CSD was analyzed in rat neocortical slices by imaging of the intrinsic optical signal. CSD was measured as the percentage of the maximal surface of a cortical slice covered by the propagation of intrinsic optical signal changes during an induction episode. Reproducible CSD episodes were induced through repetitive elevations of extracellular potassium concentration. AMPA glutamate receptor antagonism did not inhibit CSD, whereas NMDA receptor antagonism did inhibit CSD. Blockade of voltage-dependent sodium channels by TTX also reduced CSD. CSD was also decreased by the antiepileptic drug topiramate, but not by carbamazepine. Interestingly, endogenous CGRP was released in the cortical tissue in a calcium-dependent manner during CSD, and three different CGRP receptor antagonists had a dose-dependent inhibitory effect on CSD, suggesting a critical role of CGRP in this phenomenon. Our findings show that both glutamate NMDA receptors and voltage-dependent sodium channels play roles in CSD. They also demonstrate that CGRP antagonism reduces CSD, supporting the possible use of drugs targeting central CGRP receptors as antimigraine agents.M igraine is a common episodic headache disorder characterized by attacks that include various combinations of headache and neurologic, gastrointestinal, and autonomic symptoms. It is among the most common neurologic conditions, affecting ∼12-20% of the population. The International Headache Society classifies migraine into migraine without aura and migraine with aura, with aura defined as the complex of focal neurologic symptoms that most often precedes or accompanies an attack (1-3).Cortical spreading depression (CSD) is thought to represent a key pathogenetic step in migraine with aura (4, 5). First reported by Leão in 1944 (6), CSD is a wave of electrical activity (excitation followed by depression) that moves across the cerebral cortex after electrical or chemical stimulation. The pivotal event in the generation and propagation of CSD is a marked decrease in neuronal membrane resistance associated with massive increases in extracellular K + and neurotransmitters, as well as increases in intracellular Na + and Ca 2+ (7-9). Genetic and environmental factors modulate individual susceptibility by lowering the CSD threshold, and cortical excitation can cause sufficient elevation in extracellular K + and glutamate to initiate CSD (5,7,8,(10)(11)(12)(13)(14). Conversely, the CSD threshold also may be increased by factors that re...

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“…CGRP plays a crucial role in producing vasodilation and maintaining low vascular resistance by binding to the CGRP-1 receptor (Jansen-Olesen et al, 2001;Brain and Grant, 2004,). CGRP 8−37 , a classic antagonist of CGRP-1 receptor, has been used to block CGRP-induced vasodilation (Chiba et al, 1989). Intravenous or paw injection of CGRP 8−37 attenuates SCS-induced vasodilation at all intensities (Tanaka et al, 2001;.…”

Section: Antidromic Mechanism-mentioning

confidence: 99%

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

Linderoth

Foreman

2008

Autonomic Neuroscience

156

106

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Spinal cord stimulation (SCS) is a widely used clinical technique to treat ischemic pain in peripheral, cardiac and cerebral vascular diseases. The use of this treatment advanced rapidly during the late 80's and 90's, particularly in Europe. Although the clinical benefits of SCS are clear and the success rate remains high, the mechanisms are not yet completely understood. SCS at lumbar spinal segments (L2-L3) produces vasodilation in the lower limbs and feet which is mediated by antidromic activation of sensory fibers and decreased sympathetic outflow. SCS at thoracic spinal segments (T1-T2) induces several benefits including pain relief, reduction in both frequency and severity of angina attacks, and reduced short-acting nitrate intake. The benefits to the heart are not likely due to an increase, or redistribution of local blood flow, rather, they are associated with SCS-induced myocardial protection and normalization of the intrinsic cardiac nervous system. At somewhat lower cervical levels (C3-C6), SCS induces increased blood flow in the upper extremities. SCS at the upper cervical spinal segments (C1-C2) increased cerebral blood flow, which is associated with a decrease in sympathetic activity, an increase in vasomotor center activity and a release of neurohumoral factors. This review will summarize the basic science studies that have contributed to our understanding about mechanisms through which SCS produces beneficial effects when used in the treatment of vascular diseases. Furthermore, this review will particularly focus on the antidromic mechanisms of SCS-induced vasodilation in the lower limbs and feet.

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Calcitonin gene-related peptide receptor antagonist human CGRP-(8-37)

Cited by 211 publications

References 15 publications

Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

Neonatal de-afferentation of capsaicin-sensitive sensory nerves increases in vivo insulin sensitivity in conscious adult rats

Critical role of calcitonin gene-related peptide receptors in cortical spreading depression

Putative mechanisms behind effects of spinal cord stimulation on vascular diseases: A review of experimental studies

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