Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alternative splicing of the primary RNA transcript of the calcitonin gene leads to the generation of two distinct peptides, calcitonin (CT) and calcitonin gene-related peptide (CGRP). These peptides share only limited sequence homology and generally subserve different biological functions through their own distinct binding sites, which differ in specificity and distribution. Additionally, a binding site with high-affinity binding for both peptides that has a restricted pattern of distribution has been identified. The present article reviews the biochemical and morphological characteristics of centra CT and CGRP binding sites.
Mol Neurobiol 1991
PMID:Central nervous system binding sites for calcitonin and calcitonin gene-related peptide. 166 88

Several lines of evidence suggest a possible role for mast cell proteases in modulating the biologic effects of neuropeptides. To explore the potential of such interactions in human airway, we examined the activity of human tryptase, the major secretory protease of human lung mast cells, against several neuropeptides with proposed regulatory functions in human airway. Using highly purified tryptase obtained from extracts of human lung, we determined the sites and rats of hydrolysis of vasoactive intestinal peptide (VIP), peptide histidine-methionine (PHM), calcitonin gene-related peptide (CGRP), and the tachykinins substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). Tryptase hydrolyzes VIP rapidly at several sites (Arg12, Arg14, Lys20, and Lys21) with an overall kcat/Km of 1.5 x 10(5) M-1 s-1 and hydrolyzes PHM primarily at a single site (Lys20) with a kcat/Km of 1.9 x 10(4) M-1 s-1. Tryptase also rapidly hydrolyzes CGRP at two sites (Arg18 and Lys24) with a kcat/Km of 2.7 x 10(5) M-1 s-1. The tachykinins are not hydrolyzed by tryptase. These observations raise the possibility that tryptase-mediated degradation of the bronchodilators VIP and PHM combined with exaggerated mast cell release of tryptase may contribute to the increase in bronchial responsiveness and the decrease in immunoreactive VIP in airway nerves associated with asthma. The favorable rates of hydrolysis of CGRP suggest that tryptase may also terminate the effects of CGRP on bronchial and vascular smooth muscle tone and permeability.
Am J Respir Cell Mol Biol 1990 Jul
PMID:Degradation of airway neuropeptides by human lung tryptase. 169 72

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.
J Mol Neurosci 1991
PMID:Increased calcitonin gene-related peptide (CGRP), substance P, and enkephalin immunoreactivities in dorsal spinal cord and loss of CGRP-immunoreactive motoneurons in arthritic rats depend on intact peripheral nerve supply. 171 33

In situ hybridization histochemistry was used to study changes in mRNAs coding neuropeptides such as alpha-calcitonin gene-related peptide (CGRP), beta-CGRP, cholecystokinin (CCK) and galanin, in rat facial motoneurons following axotomy of the facial nerve. In control rats, 38%, 55% and 7% of the facial motoneurons expressed alpha-CGRP, beta-CGRP and CCK mRNAs, respectively. No galanin mRNA-containing motoneurons were observed in these animals. The levels of mRNA for alpha-CGRP, CCK and galanin were increased while the beta-CGRP mRNA level was decreased after axotomy. The levels of mRNAs for these peptides returned to the control values by 2-4 weeks after nerve crush, whereas nerve resection had more prolonged effects. Within 3-4 weeks after injury, nerve resection had greater effects on beta-CGRP, CCK and galanin mRNAs than did nerve crush. Thus, there appear to be differences in the regulation of mRNA expression of these peptides in axotomized motoneurons.
Brain Res Mol Brain Res 1991 Oct
PMID:Changes in expression of peptides in rat facial motoneurons after facial nerve crushing and resection. 172 91

In this study we have examined the physiological and neurochemical development of the cutaneous afferent pathways from the hindlimb to the spinal cord in fetal sheep. We have shown that somatosensory input from the hindlimb evokes activity in DRG neurons at 87d gestation and in cells in the dorsal horn at 92d (term, 146d). There is evidence of immunoreactivity for substance P, calcitonin gene-related peptide and glutamine several days prior to this at 77-80 days. The implication of these findings are discussed.
Mol Neurobiol 1991
PMID:Prenatal development of cutaneous afferent connections in the spinal cord of fetal sheep. A physiological and neurochemical study. 172 44

The spontaneous electrical activity of calcitonin-secreting cells (C-cells) appears to play an important role in the coupling of fluctuations in the extracellular Ca2+ to changes in the intracellular Ca2+ concentration and thus for calcitonin secretion. Using the patch clamp technique, we have investigated the spontaneous electrical activity and the underlying ionic currents in C-cells of the rMTC 44-2 cell line. With 1.2 mM external Ca2+, the membrane potential was -46.1 +/- 1.7 mV (n = 58) and about 30% of the cells spontaneously fired action potentials. Rising the external Ca2+ to 1.8 mM caused the cells to depolarize to -42.1 +/- 2.1 mV (n = 56) and spontaneous electrical activity was seen in about 70% of cells. Under voltage clamp conditions, tetrodotoxin-sensitive voltage-dependent Na+ currents, outward-rectifying K+ currents and isradipine-, omega-conotoxin-sensitive as well as isradipine- and omega-conotoxin-insensitive Ca2+ currents were observed. These voltage-dependent currents appear to be the major ionic currents contributing to action potentials in C-cells and to participate in calcitonin secretion.
Mol Cell Endocrinol 1991 Dec
PMID:Electrophysiological properties of rat calcitonin-secreting cells. 183 94

The chronic administration of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) to 9-day-old suckling rats induced no change on day 13 in the calcitonin (CT) mRNA steady-state level of thyroid glands measured by Northern hybridization. Thyroidal CT contents were decreased in relation to increased plasma calcium levels in animals treated with 0.1 or 1 microgram 1,25-(OH)2D3/kg. Using a lower dose (0.01 microgram/kg), neither plasma calcium, nor thyroidal CT contents were changed. No correlation was found between CT mRNA levels and thyroidal CT contents as well as for plasma CT levels and thyroidal CT contents since hormone in blood remained unchanged after treatment by the active vitamin D3 metabolite. Intraperitoneal calcium administration in fasted 13-day-old rats was associated with a 5-fold increase in plasma CT 30 min after injection, but CT mRNA levels were unchanged within 240 min. By contrast, stomach gavage with calcium in fasted 13-day-old rats induced a sustained increase in plasma CT (X2), and a 4-fold increase in the steady-state level of CT mRNA. Calcium per se is a potent stimulator of CT release in suckling rats, but did not change the amount of CT mRNA. However, gastrointestinal factors may be implied directly or indirectly in the increased CT mRNA level after calcium gavage. In conclusion, 1,25-(OH)2D3 which is known to affect CT gene expression in adult rats is ineffective in 13-day-old suckling rats. This observation may be related to developmental changes in the amount of 1,25-(OH)2D3 receptors of C cells.
Mol Cell Endocrinol 1991 Aug
PMID:Effects of 1,25-dihydroxycholecalciferol and calcium on calcitonin mRNA levels in suckling rats. 193 45

Bronchial reactivity changes during childhood, indicating possible changes in neural control. Nerves supplying the intrapulmonary airways were therefore studied in autopsy tissue from 14 normal infants (0 to 3.5 yr), 3 children (8.3 to 10.75 yr), and 4 adults (17 to 24 yr). An indirect immunofluorescence technique was used to study the distribution and relative number of nerve fibers containing the general neuronal markers protein gene product 9.5 and synaptophysin. Nerve subpopulations were identified using antisera to neuropeptide tyrosine, vasoactive intestine polypeptide, somatostatin, substance P, calcitonin gene-related peptide, and the enzyme tyrosine hydroxylase. Between birth and 3 yr, the distribution and relative number of immunoreactive nerves shown by both the general neuronal markers and specific antisera did not change. Neuropeptide tyrosine-immunoreactive nerves were the most common peptide-containing nerve subpopulation identified in the human lung, supplying bronchial smooth muscle, submucosal glands, cartilage, and submucosa. Other peptide-containing nerves exhibited distinct distribution patterns. Two differences in the airway innervation were identified between cases aged 0 to 3.5 yr and the older age groups. Relatively fewer peptide-containing nerves occurred in the adult bronchioli and respiratory unit, but the relative number of vasoactive intestinal polypeptide-containing nerves supplying the bronchial and bronchiolar smooth muscle was greater in the two older age groups. Given these apparent age-related differences in the number of peptide-containing nerves supplying the human airway, studies on the development of peptide receptors are indicated.
Am J Respir Cell Mol Biol 1990 Sep
PMID:Immunohistochemical localization of peptide-containing nerves in human airways: age-related changes. 197 91

Respiratory epithelium has been reported to be supplied with sensory nerves and to contain irritant and other receptors. In this immunohistochemical study, we examined the incidence, morphology, and distribution of calcitonin gene-related peptide (CGRP) immunoreactivity in epithelial cells the rat respiratory tract, using peroxidase anti-peroxidase (PAP) techniques. CGRP immunoreactivity was localized in capsaicin-sensitive nerve fibers and in capsaicin-nonsensitive endocrine cells occurring singly or in groups. These CGRP-immunoreactive structures reached close to or actually touched the airway lumen, were widely and abundantly present in the respiratory epithelium, and were arranged in distinct and characteristic patterns. CGRP-immunoreactive nerves innervated not only grouped cells but also single cells, and the innervation of these cells differed depending on whether they were in extrapulmonary or intrapulmonary epithelium. The specificity of the immunoreactivity was confirmed by absorption tests that excluded cross-reactivity with other peptides. The results suggest that epithelial nerve fibers and endocrine-like cells exhibiting CGRP immunoreactivity form a morphologic, and probably also a functional, complex throughout the respiratory epithelium. CGRP innervation may be related to receptor functions of respiratory epithelium.
Am J Respir Cell Mol Biol 1991 Feb
PMID:Pulmonary calcitonin gene-related peptide immunoreactivity: nerve-endocrine cell interrelationships. 199 Oct 72

We have isolated from a bovine genomic library a clone which contains the calcitonin (CT) and CT gene-related peptide (CGRP) sequences, using probes representing the human CT and CGRP sequences. Sequence analysis has identified the nucleotide sequence coding for bovine CT, its C-terminal flanking peptide and bovine CGRP. The deduced amino acid sequence of bovine CGRP revealed a significant homology with other CGRPs so far reported. It differs by only one amino acid from rat CGRP alpha and porcine CGRP, and by three and four amino acids from human CGRP beta and alpha respectively. Bovine CT has, however, only 14 out of 32 residues in common with human CT. As in the human CT precursor, the C-terminal flanking peptide of bovine CT precursor is a 21 amino acid peptide. It shares only 11 residues in common with its human counterpart. This study thus provides further evidence that CGRP, in contrast to CT and its C-terminal flanking peptide, is a highly conserved molecule.
J Mol Endocrinol 1991 Apr
PMID:Predicted structure of the bovine calcitonin gene-related peptide and the carboxy-terminal flanking peptide of bovine calcitonin precursor. 204 42


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