Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CCK-secreting WE rat medullary thyroid carcinoma cell line resembles other calcitonin-producing (C-cell) lines in that calcium, cAMP, or agents which raise cAMP, dexamethasone, and beta-adrenergic agents all stimulate peptide secretion. Unlike other C-cell lines, the WE cells respond similarly to IBMX (3-isobutyl-1-methyl-xanthine, a phosphodiesterase inhibitor) in the presence and absence of forskolin, implying that these cells secrete substances that raise cAMP levels, whose effect is accentuated by IBMX. Both CGRP and neurotensin, peptides that may be secreted by these cells, caused a small, but significant, increase in CCK secretion. It is possible that these or other secreted substances that activate adenylate cyclase are responsible for the cell's high rate of CCK secretion. Their high rate of CCK synthesis and their regulated secretion suggest that these cells will be a good model for studies of CCK expression, biosynthesis, and processing.
 ...
PMID:Regulation of cholecystokinin secretion from a rat medullary thyroid carcinoma cell line: role of calcium, cyclic nucleotides, glucocorticoids, neurotensin, and calcitonin gene-related peptide. 152 66

Hurthle cell neoplasms are though to arise from the follicular cells of the thyroid gland, although some studies suggest that they originate from the parafollicular cells. We studied tissue from five patients (three men and two women, aged 33-72 yr) with Hurthle cell neoplasms (four adenomas and one carcinoma) to determine whether Hurthle cell neoplasms have an intact TSH receptor-adenylate cyclase (AC) system and, if so, whether it differs in benign and malignant Hurthle cell and neoplasms. Binding of [125I]bovine (b) TSH and an AC response to TSH occurred in all four Hurthle cell adenomas. In three of these tumors, there was good binding and a relatively good correlation between the concentration of bTSH producing half-maximal inhibition of [125I]bTSH binding (4.8 mU/ml) and the TSH concentration causing half-maximal stimulation of AC (2.2 mU/ml). There was also a 2- to 5-fold increase in AC activity in response to bTSH (300 mU/ml), a value comparable to that which occurs in follicular thyroid neoplasms and differentiated thyroid cancers. In the fourth Hurthle cell adenoma, however, binding was low, the apparent Kd (170 mU/ml) and Km (20 mU/ml) were high, and there was only a 1.4-fold increase in AC activity in response to bTSH (300 mU/ml). In the one metastatic Hurthle cell carcinoma, there was no high affinity TSH binding or AC response to TSH. Thus, Hurthle cell neoplasms are of follicular cell origin, since benign Hurthle cell tumors have an intact TSH receptor-AC system. Malignant Hurthle cell neoplasms, like undifferentiated and medullary thyroid cancer, lack a functional TSH receptor.
 ...
PMID:Thyrotropin receptor-adenylate cyclase system in Hurthle cell neoplasms. 299 48

The effect of the adenosine A1 receptor activation on calcitonin secretion was studied in medullary thyroid carcinoma cells of the rat (rMTC 6-23). Calcitonin was determined by radioimmunoassay, intracellular cAMP by protein binding assay, intracellular calcium in fura-2 loaded single cells using microspectrofluorimetry, and calcium channel activity by patch clamp technique. The adenosine A1 receptor analogue N-6 phenylisopropyl-adenosine (PIA) (10(-10)-10(-6) M) inhibits dose-dependently glucagon (10(-7) M) and rGRH (10(-7) M) stimulated cAMP formation and calcitonin secretion. These effects were partly abolished by pretreatment with pertussis toxin (PT) (100 ng/ml). PIA (10(-10)-10(-6) M) also suppressed extracellular calcium-stimulated calcitonin secretion, rises in intracellular calcium, and calcium channel currents. PT (100 ng/ml) pretreatment again partly abolished this inhibitory effect. The addition to the medium of adenosine deaminase (0.4 U/ml) stimulated calcitonin secretion. Our results suggest that in calcitonin-secreting cells A1 receptors couple to adenylate cyclase and calcium channels via PT-sensitive G proteins and thus inhibit calcitonin secretion. Adenosine seems to act as an autocrine/paracrine factor in calcitonin-secreting cells.
 ...
PMID:Adenosine A1-receptors inhibit cAMP and Ca2+ mediated calcitonin secretion in C-cells. 855 39

A cell fine of human medullary carcinoma of the thyroid, abundantly producing calcitonin (Ct) and related hormones, has proved remarkably useful as an endocrine tumor model for the study of the secretion mechanism. This cell line (TT cell) was used in studies to elucidate the dynamics of the release of Ct and chromogranin (Cg) to culture medium. The studies evaluated the intracellular concentration of Ct and Cg and the concentration changes elicited by the protein kinase C activator, phorbol ester (TPA); the adenylate cyclase-associated protein kinase A activator, forskolin; and the calcium ionophore, A23187. In addition, immunogold labeling of Ct and Cg was carried out to investigate the ultrastructural changes resulting from the stimulations. All these secretagogues effected the release of Ct and Cg into the medium in a dose-dependent manner, and the rate of the increase in the Ct secretion was consistently and markedly higher than that of Cg in more than certain dosages of the secretagogues. Most cells contained secretory granules immunolabeled for both Ct and Cg, and a considerable decrease was noted in the poststimulation count of the granules containing both substances, with the cells retaining more Cg than Ct. The discordance may be explained by different secretory pathways of the two proteins or different rates of synthesis.
 ...
PMID:Discordant secretion of calcitonin and chromogranin in the human medullary thyroid carcinoma cell line. 3213 90