Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid hormone-like factors have been found in extracts of tumors associated with humoral hypercalcemia of malignancy, many of which are of squamous epithelial origin. Cultured, nonmalignant human keratinocytes were examined for the production of similar factors. Keratinocyte-conditioned medium from ten cultures stimulated the production of cyclic adenosine monophosphate in clonally derived rat osteosarcoma cells sensitive to parathyroid hormone. Bovine [Nle8,18, Tyr34]PTH-(3-34)NH2, a competitive inhibitor of parathyroid hormone, stopped the adenylate cyclase production stimulated by keratinocyte-conditioned medium, but antisera to parathyroid hormone had no effect on such adenylate cyclase activity. The active component of keratinocyte-conditioned medium has a molecular weight exceeding that of native parathyroid hormone. These characteristics are shared by the parathyroid hormone receptor agonists associated with humoral hypercalcemia of malignancy, which suggests that normal human keratinocytes may produce a factor related to that produced by malignant tumors associated with humoral hypercalcemia of malignancy.
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PMID:A parathyroid hormone-like protein from cultured human keratinocytes. 241 17

The role of cyclic nucleotides as intracellular second messengers mediating the excitatory chronotropic and inotropic actions of octopamine (OCT) and dopamine (DA) on the neurogenic Limulus heart was investigated. Tissue levels of cAMP, but not cGMP, were significantly increased in isolated cardiac ganglia and cardiac muscle following 10 min exposure to 10(-5) M OCT or 10(-5) M DA. In both tissues, OCT elicited larger increases in cAMP than did DA. Amine-induced cAMP accumulation in the cardiac ganglion and in the cardiac muscle was prevented by the alpha-adrenergic blocker phentolamine. The adenylate cyclase activator forskolin and the phosphodiesterase inhibitor IBMX produced amine-like chronotropic and inotropic effects when applied to the isolated heart preparation. However, the kinetics of the responses differed for the two agents. Additional pharmacological agents (RO-20-1724, papaverine, SQ 20,009, and 8-parachloro-phenylthio cAMP) also had amine-like effects but to a lesser extent. The chronotropic, but not inotropic, effects of OCT and DA were potentiated in the presence of IBMX. These data suggest that a cAMP-dependent mechanism underlies the excitatory effects of the neuromodulators OCT and DA on the Limulus heart.
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PMID:Mechanism for amine modulation of the neurogenic Limulus heart: evidence for involvement of cAMP. 244 16

1. Neurons with a receptor responded to FMRFamide (Phe-Met-Arg-Phe-NH2) were identified in the ganglion of Aplysia kurodai. Ionic mechanism and channel gating system of the FMRFamide-induced responses were investigated by current clamp and voltage clamp methods. 2. The reversal potential of FMRFamide-induced response exactly coincided with the equilibrium potential for K+. This proved that the response was produced by a specific increase in membrane permeability toward K+, exclusively. 3. The FMRFamide-induced response was not affected by the inhibitors for Ca2(+)-activated K(+)-current, i.e., TEA, apamin, and EGTA. This excluded a possibility that FMRFamide-activated K(+)-channel is a Ca2(+)-activated K(+)-channel. 4. Intracellular injection of pertussis-toxin (PTX) caused no change in either resting potential or conductance, but it irreversibly blocked the FMRFamide-induced outward current within 30 min. Similarly applied cholera toxin (CTX) showed no effect on the FMRF-amide response. 5. Intracellular application of guanosine 5'-0-(2-thiodiphosphate) (GDP beta S) caused no effect on either resting potential or conductance, but it blocked the FMRFamide-induced K(+)-current within 3 min. 6. Intracellular application of guanosine 5'-0-(3-thiotriphosphate) (GTP gamma S) alone induced a slowly developing, irreversible outward current associated with an increase in membrane conductance. However, repetitive applications of FMRFamide immediately after the start of GTP gamma S application markedly facilitated the effect of GTP gamma S on the resting membrane. 7. Intracellular application of either adenylate cyclase inhibitor (3'-deoxyadenosine) or A-kinase inhibitor (H-8) did not affect the FMRFamide-induced response. 8. It was concluded that the FMRFamide-induced K(+)-current is mediated by PTX-sensitive GTP-binding protein Gi, Go or Gk. It was also suggested that the FMRFamide-induced response is produced independently of the changes in intracellular Ca2+ or cyclic AMP.
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PMID:[The gating mechanism of K(+)-channels coupled to the FMRFamide receptor in the ganglion cells of Aplysia]. 255 80

Synthetic bovine parathyroid hormone containing the 1-34 NH2-terminal amino acids [bPTH-(1-34)] inhibits uterine contraction stimulated by a variety of agonists. Previously, we reported that the parathyroid hormone analogue [Nle8, Nle18, Tyr34]bPTH-(3-34)amide [NTA-(3-34)] antagonized this effect of bPTH-(1-34) while the analogue [Tyr34]bPTH-(7-34)amide [bPTH-(7-34)] used in this study stimulated uterine contraction. However, contrary to this previous report, bPTH-(7-34) in the present study failed to initiate a contractile response and instead resulted in an inhibitory response to the bPTH-(1-34) effect on uterine contraction in a dose-related manner. The inhibitory response of bPTH-(7-34) was further confirmed by demonstrating that this preparation of bPTH-(7-34) was capable of blocking bPTH-(1-34)-stimulated adenylate cyclase activity on particulate fractions of osteoblast-like cells from neonatal mouse calvarial. These results are consistent with those in the literature for the antagonistic effect of the 7-34 PTH fragment.
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PMID:Inhibitory effect of [Tyr34]bPTH-(7-34)-amide on bPTH-(1-34) ability to reduce uterine contraction. 263 57

The small proteoglycans (PG) of bone consist of two different molecular species: one containing one chondroitin sulfate chain (PG II) and the other, two chains (PG I). These two proteoglycans are found in many connective tissues and have Mr = 45,000 core proteins with clear differences in their NH2-terminal sequences. Using antisera produced against synthetic peptides derived from the human PG I and PG II NH2 termini, we have isolated several cDNA clones from a lambda gt11 expression library made against mRNA isolated from human bone-derived cells. The clones, which reacted with antisera to the PG II peptide, were sequenced and found to be identical with the PG II class of proteoglycan from human fibroblasts known as PG-40 or decorin. The clones reacting to the PG I antisera, however, had a unique sequence. The derived protein sequence of PG I showed sufficient homology with the PG II sequence (55% of the amino acids are identical, with most others involving chemically similar amino acid substitutions) to strongly suggest that the two proteins were the result of a gene duplication. PG II (decorin) contains one attached glycosaminoglycan chain, while PG I probably contains two chains. For this reason, we suggest that PG I be called biglycan. The biglycan protein sequence contains 368 residues (Mr = 42,510 for the complete sequence and Mr = 37,983 for the secreted form) that appears to consist predominantly of a series of 12 tandem repeats of 24 residues. The repeats are recognized by their conserved leucines (and leucine-like amino acids) in positions previously reported for a diverse collection of proteins (none of which is thought to be proteoglycans) including: two morphogenic proteins (toll and chaoptin) in the fruit fly; a yeast adenylate cyclase; and two human proteins, the von Willebrand Factor-binding platelet membrane protein, GPIb, and a rare serum protein, leucine-rich glycoprotein.
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PMID:Deduced protein sequence of bone small proteoglycan I (biglycan) shows homology with proteoglycan II (decorin) and several nonconnective tissue proteins in a variety of species. 264 39

A Schizosaccharomyces pombe gene encoding adenylate cyclase has been cloned by cross-hybridization with the Saccharomyces cerevisiae adenylate cyclase gene. The protein encoded consists of 1692 amino acids and has adenylate cyclase activity that cannot be activated by the Sa. cerevisiae RAS2 protein. Sc. pombe cyclase has a high degree of homology (approximately 60%) with the catalytic domain of Sa. cerevisiae cyclase precisely mapped by a gene-deletion analysis. A 25-40% identity is observed throughout the middle segments of approximately 1000 residues of both cyclases, large parts of which are composed of repetitions of a 23-amino acid motif similar to those found in human glycoproteins, Drosophila chaoptin, and Toll gene product. However, a segment corresponding to the NH2-terminal 620 residues of Sa. cerevisiae cyclase appears lost from Sc. pombe cyclase, and the COOH-terminal 140 residues are not well conserved between the two yeast species. Deletions involving the COOH-terminal residues of Sa. cerevisiae cyclase cause loss of activation by the RAS2 protein. These results suggest that Sc. pombe cyclase may have lost the ability to interact with RAS proteins by the loss of a regulatory site.
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PMID:Adenylate cyclases in yeast: a comparison of the genes from Schizosaccharomyces pombe and Saccharomyces cerevisiae. 266 44

A novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures was isolated from ovine hypothalamic tissues. Its amino acid sequence was revealed as: His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln- Met-Ala- Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys - NH2. The N-terminal sequence shows 68% homology with vasoactive intestinal polypeptide (VIP) but its adenylate cyclase stimulating activity was at least 1000 times greater than that of VIP. It increased release of growth hormone (GH), prolactin (PRL), corticotropin (ACTH) and luteinizing hormone (LH) from superfused rat pituitary cells at as small a dose as 10(-10)M (GH, PRL, ACTH) or 10(-9)M (LH). Whether these hypophysiotropic effects are the primary actions of the peptide or what physiological action in the pituitary is linked with the stimulation of adenylate cyclase by this peptide remains to be determined.
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PMID:Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells. 280 20

It has been shown previously that secondary structural changes of bPTH-(1-34) (synthetic amino-terminal (1-34) fragment of bovine parathyroid hormone), obtained by oxidation of the methionines 8 and 18, abolished its hypotensive but not its hypercalcemic action. Hence, it has been postulated that the various physiological effects of the hormone are mediated by different receptors that require different regions or configurations of the peptide. To further examine this hypothesis the relative sensitivity of the PTH-responsive adenylate cyclase of microvessels and tubules isolated from rabbit kidney cortex, to oxidized PTH and PTH inhibitors, was examined. In the presence of GTP, bPTH-(1-34) stimulated both microvessel and tubule adenylate cyclase in a dose-dependent fashion and with analogous affinities (ED50 = 52 nM in the microvessels and 85 nM in the tubules). Hydrogen peroxide treatment of bPTH-(1-34) resulted in the loss of the adenylate cyclase stimulating potency in the microvessels while there was substantial enzyme activation (ED50 = 900 nM) in the tubules. Oxidized PTH inhibited the untreated PTH-stimulated adenylate cyclase, suggesting that oxidized PTH still retains an affinity for vascular receptor sites. Similar treatment of the sulfur-free PTH analog [Nle8,18, Tyr34]bPTH-(1-34)NH2, where methionines have been replaced by norleucine, had little or no effect in both fractions. In the microvessels the synthetic PTH antagonist analogs [Nle8,18, Tyr34]bPTH-(3-34)NH2 and [Tyr34]bPTH-(7-34)NH2, strongly inhibited the adenylate cyclase responses to bPTH-(1-34). No inhibition was seen in the tubules with the same molar ratios of inhibitor to native PTH. Together, these results suggest strongly that the differences in the adenylate cyclase response to various PTH fragments most likely represent a difference in the structural requirements for PTH actions between microvessels and tubules.
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PMID:Structure-activity relationship of parathyroid hormone: relative sensitivity of rabbit renal microvessel and tubule adenylate cyclases to oxidized PTH and PTH inhibitors. 282 Jul 61

A new type of VIP receptor was characterized in human SUP-T1 lymphoblasts. The order of potency of unlabeled peptides, in the presence of [125I]helodermin, was: helodermin(1-35)-NH2 = helodermin(1-27)-NH2 greater than helospectin greater than VIP = PHI greater than [D-Ser2]VIP greater than [D-Asp3]VIP greater than [D-His1]VIP greater than or equal to [D-Ala4]VIP greater than or equal to secretin = GRF. This specificity was distinct from that of all VIP receptors described so far in that: (i) the affinity for helodermin (Kd = 3 nM) was higher than that of VIP (Kd = 15 nM) and PHI (Kd = 20 nM); and (ii) position 4 played an important role in ligand binding. The labeled sites were likely to be functional receptors as adenylate cyclase in crude lymphoblastic membranes (200-10,000 x g pellets) was stimulated by peptides, in the presence of GTP, with the following order of potency: helodermin(1-35)-NH2 greater than helodermin(1-27)-NH2 greater than helospectin = VIP = PHI.
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PMID:A new type of functional VIP receptor has an affinity for helodermin in human SUP-T1 lymphoblasts. 283 Jan 46

A tumor-derived factor believed to cause hypercalcemia by acting on the parathyroid hormone (PTH) receptor was recently purified, cloned, and found to have NH2-terminal sequence homology with PTH. The 1-34 region of this protein was synthesized, evaluated for its postreceptor effects on the ROS 17/2.8 cell line, and its properties were compared to 1-34 PTH. Both 1-34 human humoral hypercalcemia factor (HCF) and 1-34 PTH stimulated adenylate cyclase with an effective concentration (EC)50 of approximately 1 nM. The extent of stimulation by both peptides was equally enhanced by dexamethasone. They both had a pronounced inhibitory effect on growth in the presence of dexamethasone, with an EC50 of approximately 0.1 nM, reduced alkaline phosphatase (AP) activity by approximately 70% in the absence of dexamethasone and by approximately 80% in the presence of dexamethasone with an EC50 of 0.03 nM, and when present at a concentration of 10 nM, reduced AP mRNA levels (estimated by Northern analysis) by approximately 80% in the presence or absence of dexamethasone. Thus, in addition to similar dose-response curves for adenylate cyclase stimulation, both HCF and PTH produced identical postreceptor effects in ROS 17/2.8 cells. These effects of HCF are probably mediated by the interaction of the tumor-derived factor with the PTH receptor.
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PMID:Comparison of postreceptor effects of 1-34 human hypercalcemia factor and 1-34 human parathyroid hormone in rat osteosarcoma cells. 283 Mar 17


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