Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A recent report has shown that in vitro the RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. However, in vivo, it is well known that CGRP receptors are expressed in human coronary arteries and that a beneficial effect is observed in patients after CGRP infusion of patients with congestive cardiac failure. This contrast may be explained by the in vivo impregnation of major hormones, so we have tested if glucocorticoids were able in vitro to enhance the expression of the RAMP1/CRLR expression leading to functional CGRP receptors. The expression of RAMP1, RAMP2, CRLR, and adrenomedullin was evaluated by semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) using (33)P in human coronary arteries vascular smooth muscle cells (VSMC) cultured in the presence of dexamethasone. Under basal conditions, the CRLR mRNA was expressed, but RAMP2 mRNA was clearly more abundant than RAMP1 mRNA. Increases in CRLR and RAMP1 mRNA expressions occurred 4 h after treatment of VSMC with 10(-7) M dexamethasone and no change was found for RAMP2 mRNA. Adrenomedullin mRNA increased later, i.e., 8 and 16 h after dexamethasone treatment. The RAMP1 mRNA expression was elevated with doses of dexamethasone ranging from 10(-10) to 10(-7) M, thus a 5-fold increase in the ratio between RAMP1 and RAMP2 was observed with the lowest dose of dexamethasone and a 2-fold rise at 10(-7) M. CRLR mRNA levels were half-reduced with the two lowest doses of dexamethasone (10(-10) and 10(-9) M), but increased from 10(-8) to 10(-7) M. Thus, we suggest that, in vivo, glucocorticoids are involved in the expression of CGRP receptors by human coronary VSMC.
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PMID:Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells. 1077 50

In order to characterize the expression of adrenomedullin during pregnancy, we measured the mature and total concentrations in maternal plasma and amniotic fluid, and examined its expression in fetoplacental tissues. Plasma samples were obtained from 13 normal normotensive non-pregnant women and 14 normal normotensive post partum women. Maternal plasma and amniotic fluid samples were obtained from 37 normal pregnant women (10 in the first trimester, 13 in the second trimester and 14 in the third trimester). Fetoplacental tissues were obtained from first and third-trimester pregnancies. Mature and total adrenomedullin concentrations in plasma and amniotic fluid were determined by using specific radioimmunoassay. The distribution and expression of adrenomedullin were determined using immunohistochemistry, reverse-transcriptase polymerase chain reaction, and in situ hybridization. Plasma total adrenomedullin concentrations were increasing with advancing gestation. The mature/total adrenomedullin ratio in the second trimester was the highest during pregnancy. Mature and total adrenomedullin concentrations in the amniotic fluid were significantly higher than those in the maternal plasma throughout gestation (P< 0.05). Mature adrenomedullin concentrations and the mature/total adrenomedullin ratio in the amniotic fluid increased with advancing gestation. There was a significant linear correlation between amniotic fluid and maternal plasma mature/total adrenomedullin ratio in the first or second trimester of pregnancy. Adrenomedullin mRNA was identified in the amniotic membrane and chorionic villi, and within the endothelial layers of villous blood vessels. These results suggest that the mature/total adrenomedullin ratio is modified in maternal plasma and amniotic fluid with advancing gestation.
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PMID:Change of adrenomedullin concentrations in plasma and amniotic fluid, and human placental adrenomedullin expression with advancing gestation. 1117 Aug 30

Evidence has accumulated showing that vasoactive peptides, such as endothelin-1, adrenomedullin and urotensin-II, are expressed in various kinds of tumour cells. In the present study, the expression of endothelin-1 and endothelin receptors was studied in eight human tumour cell lines: T98G (glioblastoma), IMR-32 and NB69 (neuroblastoma), BeWo (choriocarcinoma), SW-13 (adrenocortical carcinoma), DLD-1 (colonic carcinoma), HeLa (cervical carcinoma) and VMRC-RCW (renal carcinoma). Reverse transcriptase-PCR showed expression of endothelin-1 mRNA in seven out of the eight cell lines, the exception being BeWo cells. ET(A) receptor mRNA was expressed in T98G, IMR-32 and NB69 cells, but weakly in the other cells. ET(B) receptor mRNA was expressed in IMR-32, NB69 and BeWo cells, but only weakly in T98G and HeLa cells. Immunoreactive endothelin was detected in the culture media of six out of the eight cell lines, but not in that of IMR-32 or BeWo cells. Treatment of T98G cells with an anti-endothelin-1 antibody or an anti-adrenomedullin antibody for 24 h decreased cell numbers to approx. 84% and 90% of control respectively. Treatment with the ET(A) receptor antagonist BQ-610 (1 microM) significantly decreased cell number to about 90% of control, whereas the ET(B) receptor antagonist BQ-788 had no significant effect. On the other hand, exogenously added endothelin-1, adrenomedullin or urotensin-II (0.1 microM) had no significant effects on cell number. These results suggest that endothelin-1 acts as a paracrine or autocrine growth stimulator in tumours. The effect of endothelin-1 on tumour growth appears to be mediated by the ET(A) receptor.
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PMID:Three vasoactive peptides, endothelin-1, adrenomedullin and urotensin-II, in human tumour cell lines of different origin: expression and effects on proliferation. 1219 50

The purpose of the present study was to characterize the effects of human (h) alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries from man and to investigate the presence of mRNA for the calcitonin receptor like receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3, in cerebral and middle meningeal arteries with and without endothelium, in microvessels and in the endothelial cells isolated from the human basilar artery. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with and without endothelium as well as in microvessels and in the endothelial cells. Human and rat alpha- and beta-CGRP, amylin, adrenomedullin and [acetamidomethyl-Cys(2,7)]human CGRP induced strong concentration-dependent relaxation of human cerebral and middle meningeal arteries. Removal of the endothelium neither changed the maximum relaxant response nor the pIC(50) values for alpha- and beta-CGRP as compared to the responses in arteries with an intact endothelium. Human alpha-CGRP-(8-37) caused a shift of h alpha- and h beta-CGRP-induced relaxations in cerebral and middle meningeal arteries. Calculation of pK(B) values revealed that h alpha-CGRP-(8-37) could not significantly discriminate between relaxations induced by h alpha-CGRP (pK(B) around 6.8) and h beta-CGRP (pK(B) around 5.4). There was no significant difference in pK(B) value of h alpha-CGRP-(8-37) on h beta-CGRP-induced relaxation of human cerebral and middle meningeal arteries with and without endothelium. In conclusion, our molecular and pharmacological data support the existence of a single type of CGRP(1) receptors in the human intracranial circulation.
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PMID:In-depth characterization of CGRP receptors in human intracranial arteries. 1464 88