Disease relevance of CALCA

• CGRP up to 800 pmol/kg did not change blood pressure but produced a pronounced tachycardia [1].

High impact information on CALCA

• In a search for the second messengers involved, we now demonstrate that CGRP stimulates accumulation of cyclic AMP (cAMP) in cultured chick myotubes [2].
• The present findings suggest that cAMP is one of the second messengers which mediate the increase in acetylcholine receptor number elicited by CGRP [2].
• Furthermore, CGRP might be implicated in other trophic actions mediated by cAMP in skeletal muscle cells [2].
• Thus, the cells costore 5-HT with calcitonin, not calcitonin gene-related peptide (CGRP), which is the product of the calcitonin gene expressed in neurons, and they do not contain neurofilaments [3].
• The addition of beta-NGF to the cultured parafollicular cells induced a number of them to extend neurites and increased the proportion of cells in which CGRP immunoreactivity could be found [3].

Biological context of CALCA

• The highest density of CGRP binding sites was detected on the smooth muscle; venules and arterioles expressed moderate binding [4].
• To elucidate the possible functional significance of sensory neuropeptides in visceral organs of mammals and birds the distribution, binding sites and the effects on ureteric peristalsis of substance P and calcitonin gene-related peptide (CGRP) were investigated in the ureter of guinea-pigs and chickens [4].
• Calcitonin mRNA and calcitonin gene-related peptide (CGRP) mRNA both are generated from the calcitonin gene because of tissue-specific alternative splicing of the primary transcript [5].
• While CGRP mRNA is first expressed in motor neurons at rather advanced stages of embryogenesis, calcitonin mRNA is expressed in the floor plate and dorsal rhombencephalon from earliest stages [5].
• This demonstrates that the control of the onset of CGRP expression is unlikely to be linked to processes which are regulated by neuromuscular transmission including naturally-occurring cell death [6].

Anatomical context of CALCA

• Fluorescence triple-labeling of COX-2, SP and calcitonin gene-related peptide (CGRP) confirmed that the majority of these SP-containing elements coexisted with CGRP, indicating that these elements originated from primary afferent neurons [7].
• Calcitonin is expressed predominantly in ultimobranchial bodies and CGRP in brain [8].
• Moreover, CGRP causes an increase in the number of acetylcholine receptors on the surface of cultured chick myotubes [2].
• This correlation between the presence of SP or CGRP in a neuron and a particular functional modality thus provides evidence for a functional distinction between the mediodorsal and ventrolateral zones that are apparent during the development of chick dorsal root ganglia [9].
• Distribution and ontogeny of SP, CGRP, SOM, and VIP in chick sensory and sympathetic ganglia [9].

Associations of CALCA with chemical compounds

• Recent immunocytochemical studies have shown that calcitonin gene-related peptide (CGRP) coexists with the neurotransmitter acetylcholine in spinal motoneurons of the chick [2].
• The peristalsis frequency of the isolated ureter of the guinea-pig was increased by neurokinin A and substance P, whereas CGRP inhibited ureteric motility [4].
• Moreover, the effect of CGRP was independent of the one produced by tetrodotoxin, a blocker of membrane electrical activity but not of that caused by cholera toxin, an activator of adenylate cyclase [10].
• 2. Relaxation to CGRP 10(-8) M was reduced by 86.4+/-5.2% by the CGRP-1 receptor antagonist CGRP8-37 (10(-6) M), but unaffected by NG-nitro-L-arginine (10(-4) M), indomethacin (10(-6) M) and by removal of the endothelium, suggesting no involvement of nitric oxide, prostaglandins or endothelium-derived factors [11].
• CGRP infusions caused significantly more rapid restoration of tissue ATP levels and resulted in a smaller rise in blood thromboxane as compared with controls [12].

Other interactions of CALCA

• In close proximity, there were larger (40 microm) unlabeled neurons that were positive for ChAT and CGRP, but negative for GAL [13].

Analytical, diagnostic and therapeutic context of CALCA

• As a first step toward investigating the function of CGRP in birds, its distribution was studied in the domestic chick and quail brain by means of immunocytochemistry, by using antibodies against rat CGRP [14].
• To examine whether embryonic DRG cells respond to activin we treated dissociated cultures of DRG with activin A and assessed the expression of vasoactive intestinal peptide (VIP) and calcitonin gene related peptide (CGRP) mRNAs using semiquantitative rtPCR [15].
• Two transcripts encoding AChE, approximately 4.8 and approximately 6.0 kb, were identified and their levels of expression were increased to approximately 3-fold after treatment with CGRP [16].
• Infusions of a novel calcitonin gene-related peptide (CGRP) derivative at the time of reperfusion to salvage ischaemic rabbit skin flaps [12].

References