The role of the sensory peptide calcitonin-gene-related peptide(s) in skeletal muscle carbohydrate metabolism: effects of capsaicin and resiniferatoxin

1. The content of calcitonin-gene-related-peptide-like immunoreactivity (CGRP-LI) in various rat muscles was measured. Starvation for 24 h did not affect the content of CGRP-LI in these muscles, except for a decreased level in the starved-rat diaphragm. Higher contents of CGRP-LI were observed in well-vascularized muscles. 2. Capsaicin (at 1, 10 and 100 microM) inhibited insulin-stimulated rates of glycogen synthesis in isolated stripped incubated soleus muscle preparations by a mechanism independent of catecholamine release, since the effects of capsaicin were not altered by the beta-adrenoreceptor antagonist DL-propranolol. 3. Resiniferatoxin (10 nM), which is a potent capsaicin agonist, also significantly inhibited the insulin-stimulated rate of glycogen synthesis. Furthermore, the concentration of resiniferatoxin required to inhibit glycogen synthesis was 100 times less than the concentration of capsaicin needed for the same effect. 4. Capsaicin (10 microM) decreased the content of CGRP-LI in isolated stripped incubated soleus muscle preparations by about 40%. 5. Neonatal treatment of rats with capsaicin, which causes de-afferentation of some sensory nerves such, we hypothesize, that CGRP can no longer be released to counteract the effects of insulin in vivo, caused increased rates of glycogen synthesis and increased glycogen content in stripped soleus muscle preparations in vitro when muscles were isolated from the adult rats. 6. These findings support the hypothesis that capsaicin and resiniferatoxin elicit an excitatory response on sensory nerves in skeletal muscle in vitro to cause the efferent release of CGRP. Consequently, CGRP is delivered to skeletal muscle fibres to inhibit insulin-stimulated glycogen synthesis. The role of CGRP in recovery of blood glucose levels during hypoglycaemia is discussed.

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Local neurogenic regulation of rat hindlimb circulation: role of calcitonin gene-related peptide in vasodilatation after skeletal muscle contraction

British Journal of Pharmacology ◽

10.1038/sj.bjp.0701422 ◽

1997 ◽

Vol 122 (4) ◽

pp. 703-709 ◽

Cited By ~ 24

Author(s):

Masami Yamada ◽

Tomohisa Ishikawa ◽

Akira Fujimori ◽

Katsutoshi Goto

Keyword(s):

Skeletal Muscle ◽

Muscle Contraction ◽

Calcitonin Gene Related Peptide ◽

Related Peptide ◽

Skeletal Muscle Contraction ◽

Calcitonin Gene

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Mechanism by which calcitonin gene-related peptide antagonizes insulin action in vivo

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.2.e321 ◽

1991 ◽

Vol 260 (2) ◽

pp. E321-E325 ◽

Cited By ~ 4

Author(s):

S. B. Choi ◽

S. Frontoni ◽

L. Rossetti

Keyword(s):

Skeletal Muscle ◽

Insulin Action ◽

Hepatic Glucose Production ◽

Glycogen Synthesis ◽

Calcitonin Gene Related Peptide ◽

Whole Body ◽

Related Peptide ◽

Calcitonin Gene ◽

Clamp Study

Calcitonin gene-related peptide (CGRP) is a peptide with structural homology to amylin, which is present in nerve terminals of skeletal muscle and intestine. The effect of this peptide on in vivo insulin action was studied in conscious rats. All rats received 180 min euglycemic (5.6 mM) insulin (21.5 pmol.kg-1.min-1) clamp study in combination with [3-3H]- and [U-14C]glucose infusions. In the basal state, the plasma CGRP concentration was 36 +/- 5 pM, and the skeletal muscle CGRP concentration was 376 +/- 88 pmol/kg wet wt. CGRP was infused at 100 pmol.kg-1.min-1 during the last 90 min of the insulin clamp study and determined a rise in plasma concentration to 781 +/- 34 pM. Hepatic glucose production was stimulated by the infusion of CGRP (35.6 +/- 6.1 vs. 24.4 +/- 4.4 mumol.kg-1.min-1). During infusion in insulin alone, glucose uptake was 133.3 +/- 8.9 mumol.kg-1.min-1 and decreased to 105.5 +/- 12.2 mumol.kg-1.min-1 with CGRP. However, the whole body rates of glycolysis (3H2O generation) were higher during the infusion of CGRP (83.9 +/- 6.1 mumol.kg-1.min-1) compared with insulin alone (72.2 +/- 7.8 mumol.kg-1.min-1). By contrast, CGRP determined a severe impairment in muscle glycogen synthesis (11.7 +/- 3.9 vs. 47.8 +/- 5.0 mumol.kg-1.min-1). Skeletal muscle glucose 6-phosphate concentration was significantly increased after CGRP infusion compared with insulin alone (0.540 +/- 0.052 vs. 0.219 +/- 0.038 mumol/g wet wt; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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Pancreatic amylin and calcitonin gene-related peptide cause resistance to insulin in skeletal muscle in vitro

Nature ◽

10.1038/335632a0 ◽

1988 ◽

Vol 335 (6191) ◽

pp. 632-635 ◽

Cited By ~ 346

Author(s):

Brendan Leighton ◽

Garth J. S. Cooper

Keyword(s):

Skeletal Muscle ◽

Calcitonin Gene Related Peptide ◽

Related Peptide ◽

Calcitonin Gene ◽

Resistance To Insulin

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Effect of Sympathetic and Parasympathetic Mediators on the Release of Calcitonin Gene-Related Peptide and Prostaglandin E2 from Rat Dura Mater, in vitro

Cephalalgia ◽

10.1111/j.1468-2982.2005.01035.x ◽

2006 ◽

Vol 26 (3) ◽

pp. 282-289 ◽

Cited By ~ 15

Author(s):

A Ebersberger ◽

H Takac ◽

F Richter ◽

H-G Schaible

Keyword(s):

Dura Mater ◽

Calcitonin Gene Related Peptide ◽

Sensory Nerves ◽

Current Debate ◽

Prostaglandin E ◽

Contact Site ◽

Related Peptide ◽

Calcitonin Gene ◽

Basal Release

Although not without controversy, an influence of the autonomic nervous system in headache is a matter for current debate. A possible contact site of autonomic and sensory nerves is the dura mater, where they form a dense network accompanying blood vessels. We investigated interactions between autonomic and nociceptive fibres by measuring release of calcitonin gene-related peptide (CGRP) and prostaglandin E2 (PGE2) from the dura mater, in vitro. The parasympathomimetic agent carbachol did not change basal release of CGRP or PGE2, whereas it diminished release induced by a mixture of inflammatory mediators. Norepinephrine did not change induced release of CGRP or PGE2, nor basal release of CGRP. However, basal release of PGE2 was enhanced by norepinephrine, and this enhancement was reduced by serotonin through 5-HT1D receptors. We conclude that sympathetic transmitters may control nociceptor sensitivity via increased basal PGE2 levels, a possible mechanism to facilitate headache generation. Parasympathetic transmitters may reduce enhanced nociceptor activity.

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Role of calcitonin gene-related peptide in the postischemic anti-inflammatory effects of antecedent ethanol ingestion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00839.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. H531-H537 ◽

Cited By ~ 13

Author(s):

Kazuhiro Kamada ◽

F. Spencer Gaskin ◽

Taiji Yamaguchi ◽

Patsy Carter ◽

Toshikazu Yoshikawa ◽

...

Keyword(s):

Peak Plasma ◽

Sensory Nerve ◽

Calcitonin Gene Related Peptide ◽

Sensory Nerves ◽

Ethanol Ingestion ◽

Related Peptide ◽

Calcitonin Gene ◽

Inflammatory Phenotype ◽

Anti Inflammatory

The aim of this study was to determine the role of calcitonin gene-related peptide (CGRP) in the postischemic anti-inflammatory effects of antecedent ethanol ingestion. Ethanol was administered to wild-type C57BL/6 mice on day 1 as a bolus by gavage at a dose that produces a peak plasma ethanol of 45 mg/dl 30 min after administration. Twenty-four hours later ( day 2), the superior mesenteric artery was occluded for 45 min followed by 70 min of reperfusion (I/R). Intravital fluorescence microscopy was used to quantify the numbers of rolling (LR) and adherent (LA) leukocytes labeled with carboxyfluorescein diacetate succinimidyl ester in postcapillary venules of the small intestine. I/R increased LR and LA, effects that were prevented by antecedent ethanol. The postischemic anti-inflammatory effects of ethanol consumption were abolished by administration of a specific CGRP receptor antagonist [CGRP-(8–37)] or after sensory nerve neurotransmitter depletion using capsaicin administered 4 days before ethanol ingestion, which initially induces rapid release of CGRP from sensory nerves, thereby depleting stored neuropeptide. Administration of exogenous CGRP or induction of endogenous CGRP release by treatment with capsaicin 24 h before I/R mimicked the postischemic anti-inflammatory effects of antecedent ethanol ingestion. Preconditioning with capsaicin 24 h before I/R was prevented by coincident treatment with CGRP-(8–37), while exogenous CGRP induced an anti-inflammatory phenotype in mice depleted of CGRP by capsaicin administration 4 days earlier. Our results indicate that the effect of antecedent ethanol ingestion to prevent postischemic LR and LA is initiated by a CGRP-dependent mechanism.

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