Release and effects of calcitonin gene-related peptide in myocardial ischaemia

Källner, Göran

doi:10.1080/140174398427956

Cited by 30 publications

(4 citation statements)

References 170 publications

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“…The α-and β-CGRP isoforms are encoded in different genes and differ from each other in rats or humans in only one or three amino acids (Kallner 1998). Both α-and β-CGRP are synthesized in the cell bodies of primary sensory neurons and transported axonally mainly to peripheral, but also to central nerve terminals, where they are stored in large, dense-cored secretory granules (Kallner 257 Fig.…”

Section: Discussionmentioning

confidence: 99%

Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide

Zhou

Peng

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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Previous investigations have demonstrated that early preconditioning induced by nitroglycerin is mediated by calcitonin gene-related peptide (CGRP). In the present study, we addressed the question of whether delayed preconditioning induced by nitroglycerin in the rat is related to stimulation of the release and synthesis of CGRP. Sprague-Dawley rats were pretreated with nitroglycerin 24 h before the experiment. The left main coronary artery was occluded for 60 min, followed by 3 h reperfusion. Infarct size, serum creatine kinase activity, serum levels of NO and CGRP and the expression of alpha- and beta-CGRP isoform mRNA in lumbar dorsal root ganglia were measured. Pretreatment with nitroglycerin (60 or 120 microg/kg i.v.) reduced both the infarct size and the release of creatine kinase during reperfusion and caused a significant increase in the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA, concomitantly with an increase in concentrations of NO and CGRP. The increase in CGRP expression preceded the increase in CGRP release. The effects of nitroglycerin were abolished completely by pretreatment with methylene blue (30 mg/kg i.p.), an inhibitor of guanylate cyclase, or capsaicin (50 mg/kg s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves. The present results suggest that the delayed cardioprotection induced by nitroglycerin is mediated mainly by the alpha-CGRP isoform via the NO-cGMP pathway.

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Section: Discussionmentioning

confidence: 99%

Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide

Zhou

Peng

et al. 2002

Naunyn-Schmiedeberg's Archives of Pharmacology

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“…CGRP is released from the heart in laboratory species in response to ischemia and low pH (105), with evidence that endothelium-derived prostacyclin (PGI 2 ) may also play a role in CGRP release (178). Infusion of CGRP was shown to attenuate and delay ischemia reperfusion arrythmias in the anesthetized rat (397), and these beneficial effects have been shown to be inhibited by CGRP 8 -37 in vitro (222).…”

Section: A Cgrp: a Protective Factor?mentioning

confidence: 97%

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Brain

Grant

2004

Physiological Reviews

669

542

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This review summarizes the receptor-mediated vascular activities of calcitonin gene-related peptide (CGRP) and the structurally related peptide adrenomedullin (AM). CGRP is a 37-amino acid neuropeptide, primarily released from sensory nerves, whilst AM is produced by stimulated vascular cells, and amylin is secreted from the pancreas. They share vasodilator activity, albeit to varying extents depending on species and tissue. In particular, CGRP has potent activity in the cerebral circulation, which is possibly relevant to the pathology of migraine, whilst vascular sources of AM contribute to dysfunction in cardiovascular disease. Both peptides exhibit potent activity in microvascular beds. All three peptides can act on a family of CGRP receptors that consist of calcitonin receptor-like receptor (CL) linked to one of three receptor activity-modifying proteins (RAMPs) that are essential for functional activity. The association of CL with RAMP1 produces a CGRP receptor, with RAMP2 an AM receptor and with RAMP3 a CGRP/AM receptor. Evidence for the selective activity of the first nonpeptide CGRP antagonist BIBN4096BS for the CGRP receptor is presented. The cardiovascular activity of these peptides in a range of species and in human clinical conditions is detailed, and potential therapeutic applications based on use of antagonists and gene targeting of agonists are discussed.

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“…Upon activation of Cfibres during ischaemia, orthodromic impulses mediate the perception of pain, whereas antidromic impulses elicit CGRP release from the peripheral nerve endings (Jancsó et al 1977). The significance of the release of sensory neuropeptides from the stimulated sensory nerve terminals has been confirmed by the detection of these peptides at the site of preconditioning (Källner 1998;Brzozowski et al 2004) and in the bloodstream (Chai et al 2006), which is presumed to contribute to the transduction of precondition- Fig. 5 Changes in secondary leukocyte-endothelial cell interactions (sticking) in postcapillary venules of the tibial periosteum in rats subjected to a 60-min ischaemia followed by 180 min of reperfusion (IR); to IPC+IR (two cycles of 10 min of complete limb ischaemia and 10 min of reperfusion before IR); to hCGRP administration (0.3 μg kg −1 , i.v., prior to ischaemia); to RTX pretreatment (3× 15 μg kg −1 , s.c., 2 weeks before IR); or to CGRP 8-37 treatment (30 μg kg −1 h −1 , i.v., during the reperfusion period).…”

Section: Discussionmentioning

confidence: 92%

“…substance P and neurokinin A (Maggi 1995). CGRP and substance P released have already been addressed as mediators of preconditioning in animal (Ferdinandy et al 1997;Wang and Wang 2005) and human tissues (Källner 1998;Brzozowski et al 2004). It has been shown that substance P-mediated vasodilation is diminished after heart IR and restored by IPC (Chlopicki et al 1999).…”

Section: Discussionmentioning

confidence: 97%

Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats

Hartmann

Varga

Zobolyák

et al. 2010

Naunyn-Schmied Arch Pharmacol

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We have shown that ischaemic preconditioning ameliorates both the local periosteal and the systemic leukocyte activation evoked by limb ischaemia-reperfusion. We hypothesized that the activation of chemosensitive afferent nerves by transient ischaemia contributes to the protective mechanisms of ischaemic preconditioning via a calcitonin gene-related peptide (CGRP)-dependent mechanism. In Sprague-Dawley rats, 60-min complete limb ischaemia was followed by 180 min of reperfusion. In further experiments, the CGRP analogue hCGRP (0.3 μg kg(-1)) or ischaemic preconditioning (2 × 10-min ischaemia/10-min reperfusion) was applied prior to the ischaemia-reperfusion insult. Ischaemic preconditioning was performed in three subgroups in which animals received the CGRP receptor antagonist CGRP(8-37) (30 μg kg(-1) h(-1)), the chemosensitive afferent nerve inactivator resiniferatoxin (3 × 15 μg kg(-1), sc), or vehicle. The effects of CGRP(8-37) and resiniferatoxin on ischaemia-reperfusion without ischaemic preconditioning were also evaluated. In the tibial periosteum of rats, intravital fluorescence microscopy and immunohistochemistry revealed significant attenuations of ischaemia-reperfusion-induced post-ischaemic leukocyte-endothelial interactions (rolling and adherence in the postcapillary venules) and tissue intracellular adhesion molecule expression following ischaemic preconditioning or hCGRP administration. Administration of CGRP(8-37) or pretreatment of animals with resiniferatoxin reversed the anti-inflammatory effects of limb ischaemic preconditioning, but failed to affect the microcirculatory consequences of ischaemia-reperfusion without ischaemic preconditioning. The results suggest that activation of the chemo- (capsaicin-) sensitive afferent nerves is involved in the mechanisms of microcirculatory anti-inflammatory protection provided by limb ischaemic preconditioning. Controlled activation of chemosensitive C-fibres or the CGRP receptors by the induction of ischaemic preconditioning or other means may furnish therapeutic benefit by ameliorating the periosteal microcirculatory consequences of tourniquet ischaemia.

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Release and effects of calcitonin gene-related peptide in myocardial ischaemia

Cited by 30 publications

References 170 publications

Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide

Delayed cardioprotection induced by nitroglycerin is mediated by alpha-calcitonin gene-related peptide

Vascular Actions of Calcitonin Gene-Related Peptide and Adrenomedullin

Anti-inflammatory effects of limb ischaemic preconditioning are mediated by sensory nerve activation in rats

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