Canadian journal of physiology and pharmacology
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Can. J. Physiol. Pharmacol. · Jul 1995
ReviewPlasticity of calcitonin gene related peptide neurotransmission in the spinal cord during peripheral inflammation.
Injection of complete Freund's adjuvant (CFA; 75 microL) 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. ⋯ 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.
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Can. J. Physiol. Pharmacol. · Jul 1995
ReviewAstrocytes and microglia as potential targets for calcitonin gene related peptide in the central nervous system.
Injury of peripheral motoneurons leads to the activation of astrocytes and microglia in the vicinity of the damaged neurons in the central nervous system. It has been proposed that neuropeptides such as the calcitonin gene related peptide (CGRP), which show an increased expression in motoneurons following axotomy, play a role as signalling molecules mediating the interactions between the damaged neurons and surrounding glial cells. Evidence supporting this hypothesis is provided by in vitro investigations of the actions of neuropeptides on glial cells. ⋯ In addition to its stimulation of immediate early gene expression, treatment of astrocyte cultures with CGRP stimulated release of the tissue plasminogen activator and led to the accumulation of mRNAs for tissue plasminogen activator and the plasminogen activator inhibitor 1. These components of the plasminogen activator system, which has been implicated in processes of tissue remodelling, are upregulated in astrocytes in the facial nucleus in vivo after facial nerve axotomy. The data suggest a role for CGRP as a mediator of glial cell activation following motoneuron injury.
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Can. J. Physiol. Pharmacol. · Jul 1995
Calcitonin gene related peptide released from dural nerve fibers mediates increase of meningeal blood flow in the rat.
The parietal dura mater encephali of the rat was shown by immunohistochemistry to be densely innervated by calcitonin gene related peptide (CGRP) immunoreactive nerve fibers spreading around the medial meningeal artery and its branches. Electrical stimulation of the dural surface (10-20 V, 5-10 Hz, 10-30 min) caused a depletion of CGRP-immunopositive fibers, suggesting a release of CGRP. The dural blood flow around branches of the medial meningeal artery was also monitored with a laser Doppler flowmeter. ⋯ This evoked increase could dose dependently be inhibited by topical application of the CGRP antagonist hCGRP8-37. Accordingly, administration of hCGRP increased the basal blood flow. We conclude that stimulation of trigeminal afferents innervating the dura mater releases CGRP from peptidergic afferent terminals, thereby causing vasodilatation and increasing the meningeal blood flow, an important element of neurogenic inflammation.
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Can. J. Physiol. Pharmacol. · Jul 1995
Alteration of calcitonin gene related peptide and its receptor binding sites during the development of tolerance to mu and delta opioids.
Calcitonin gene related peptide (CGRP), one of the most abundant peptides in the spinal cord, is localized in primary afferents and released following nociceptive stimuli. Its colocalization and corelease with substance P, a well-known nociceptive neuropeptide, support the importance of CGRP in pain mechanisms. However, its distinctive function in that regard remains to be fully established. ⋯ Similar effects were observed following a treatment with the delta agonist, DPDPE, while the kappa agonist, U-50488H, apparently only slightly decreased [125I]CGRP alpha] binding in lamina II. Binding in other laminae and CGRP-like immunostaining were not affected. These results suggest a specific interaction between spinal CGRP systems and the development of tolerance to the spinal antinociceptive effects of mu- and delta-related agonists.
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Can. J. Physiol. Pharmacol. · Jul 1995
Differential antagonism of amylin's metabolic and vascular actions with amylin receptor antagonists.
High affinity amylin binding sites are present in the rat nucleus accumbens. These sites bind [125I]amylin with an affinity of 27 pM and have high affinity for salmon calcitonin (sCT) and moderately high affinity for calcitonin gene related peptide (CGRP). N-terminally truncated peptides were tested for their ability to compete for [125I]amylin binding to these sites and to antagonize the metabolic and vascular actions of amylin. ⋯ In contrast, CGRP(8-37) was the most potent peptide at antagonizing amylin-induced hypotension in rats. Amylin's hypotensive actions appear to be mediated by a weak action at CGRP receptors, while its metabolic actions are mediated by receptors with a distinct antagonist profile. AC187 is a potent antagonist of amylin binding sites in nucleus accumbens and of amylin's metabolic actions.