Disease relevance of CALCB

• Calcitonin gene-related peptide II, substance P and vasoactive intestinal peptide in plasma and synovial fluid from patients with inflammatory joint disease [1].
• DESIGN--The effects of CGRP II (or beta), 12.5 micrograms.h-1, given by intravenous infusion for 24 h to digitalised patients with congestive heart failure, were assessed by measurement of cardiac functional indices [2].
• The present study reveals that cystein2,7 ethyl-amidealphaCGRP (Cys2,7EtalphaCGRP), an advertised calcitonin gene-related peptide 2 (CGRP2) receptor subtype-selective agonist, is also a potent agonist for the calcitonin gene-related peptide 1 (CGRP1) receptors natively expressed in the SK-N-MC human neuroblastoma cell line [3].
• The content of CGRP-2, substance P, and somatostatin in adenomas correlated directly with that of parathyroid hormone [4].

High impact information on CALCB

• In conclusion, CGRP II, unlike CGRP I, inhibits gastric acid secretion in humans [5].
• However, CGRP II and calcitonin inhibited pentagastrin-stimulated acid responses by 20% and 28%, respectively (p less than 0.05 and p less than 0.01), whereas basal acid output was only reduced with calcitonin (p less than 0.05) [5].
• The inhibitory effects of CGRP II and calcitonin are not due to increased gastric alkaline secretion or to somatostatin release, as neither peptide stimulated gastric bicarbonate secretion or induced an increase in circulating somatostatin [5].
• Thus, among the three CGRP8-37-insensitive receptors, CTR2/RAMP1 is most sensitive to the two linear analogs, suggesting that it could be classified as a CGRP2 receptor [6].
• Nucleotide sequence analysis of cloned cDNA from this cell line confirmed the production of CGRP-II mRNA [7].

Biological context of CALCB

• Stimulation of calcitonin/CGRP-I and CGRP-II gene expression by dibutyryl cAMP in a human medullary thyroid carcinoma (TT) cell line [8].
• Human INSC gene, closely linked to CALCB gene with an interval of about 30 kb, was assigned to human chromosome 11p15.2-p15 [9].
• Tachyphylaxis and cross tachyphylaxis to the effects of CGRP I and CGRP II were observed [10].
• One expresses by tissue-specific alternate splicing calcitonin and CGRP I mRNAs, the other CGRP II mRNA [11].
• Specific and saturable binding sites of the synthetic human calcitonin gene-related peptide-I (CGRP-I) and -II (CGRP-II) have been identified in membrane homogenates of the human central nervous system, heart and spleen [12].

Anatomical context of CALCB

• In a human medullary thyroid carcinoma (TT) cell line, expression of the calcitonin (CT)/CT gene-related peptide (CGRP-I) gene (CALC-I or alpha) at the level of mRNA and of encoded peptides is higher than that of the closely related CGRP-II gene (CALC-II or beta) [8].
• These are distinct CGRP2-like and amylin receptors on guinea-pig vas deferens [13].
• In the present study, human CGRP I and II exerted positive inotropic effects on isolated human right auricles and relaxed small arteries from human skeletal muscle precontracted with norepinephrine (EC50 for CGRP I 0.59 nM and for CGRP II 0.37 nM) [14].
• CGRP-II caused a monophasic increase in the IOP and disruption of the blood-aqueous barrier, but no increase in the cAMP content occurred [15].
• [Pro14]-h-alpha-CGRP, predictably, has significantly lower helical content and is a 20-fold less potent agonist on coronary artery, known to contain CGRP-1 receptor subtypes, and an antagonist on pancreatic acini, known to contain CGRP-2 receptor subtypes [16].

Associations of CALCB with chemical compounds

• In response to 1 mM dibutyryl cAMP ((Bu)2cAMP), mature CGRP-II mRNA and intact cellular CGRP-II were raised 65- and 10-fold, respectively, at 72 h [8].
• In addition to human CGRPI, human CGRPII and salmon CT stimulated the adenylate cyclase activity [17].
• Plasma CGRP II, substance P and VIP-like immunoreactivity levels showed no significant differences among patients in the three different groups of arthritis [1].
• The fall in IAS tension caused by CGRP II (human) was not modified by the neurotoxin tetrodotoxin, beta adrenoceptor antagonist propranolol and prostaglandin synthesis inhibitor indomethacin [18].
• Two amino acid differences were detected at position 1, with Gly in rabbit CGRP instead of Ala in human CGRP-II, and at position 35, with Glu instead of Lys, respectively [19].

Regulatory relationships of CALCB

• We conclude that, in addition to the previously characterized direct smooth muscle relaxant action via CGRP1 receptors (Maggi et al. Regulatory Peptides 61, 27-36, 1996), CGRP also induces a remarkable potentiation of excitatory neurotransmission to the circular muscle of the guinea-pig colon via CGRP2 receptors [20].

Other interactions of CALCB

• Real-time PCR experiments confirm the altered expression of two neuropeptides, CALCB and NPY [21].
• Human CGRP I more potently stimulated blood flow through the skin and carotid artery (p less than 0.01), and the heart rate (p less than 0.05), and plasma renin activity and aldosterone secretion than human CGRP II (p less than 0.02) [22].

Analytical, diagnostic and therapeutic context of CALCB

• Molecular cloning and expression of equine calcitonin, calcitonin gene-related peptide-I, and calcitonin gene-related peptide-II [23].
• The present study was undertaken to compare in healthy volunteers the effects of intravenous infusions of CGRP I and CGRP II (79 pmol/kg.h) on pentagastrin-stimulated acid secretion to those of calcitonin (88 pmol/kg.h) [5].

References