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

---

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

Lysine occupies position 13 in the parathyroid hormone (PTH) antagonist, [Nle8,18,Tyr34]bPTH(7-34)NH2. Acylation of the epsilon-amino group in lysine 13 by a hydrophobic moiety is well tolerated in terms of bioactivity: the analog [Nle8,18, D-Trp12,Lys 13 (epsilon-3-phenylpropanoyl),Tyr34]bPTH(7-34)NH2 is equivalent to the parent peptide in its affinity for PTH receptors and its ability to inhibit PTH-stimulated adenylate cyclase in both kidney- and bone-based assays. Truncation of this peptide by deletion of phenylalanyl7 with concomitant removal of the amino-terminal alpha-amino group yielded the analog desamino[Nle8,18,D-Trp12,Lys13 (epsilon-3-phenylpropanoyl),Tyr34]bPTH(8-34)NH2, an antagonist of high potency in vitro (Kb = 4 and 9 nM, Ki = 73 and 3.5 nM in kidney- and bone-based assays, respectively). Also this analog is potentially stable to aminopeptidases present in many biological systems.
...
PMID:Biological activity of parathyroid hormone antagonists substituted at position 13. 164 4

A high density (in the pmol/mg protein range) of specific functional receptors for PACAP (pituitary adenylate cyclase activating polypeptide) was observed in membranes from rat brain cortex, olfactory bulb, hypothalamus, hippocampus, striatum, cerebellum, pons and cervico-dorsal spinal cord, using [125I]PACAP-27 (PACAP 1-27). The tracer bound rapidly, specifically and reversibly. Competition binding curves were compatible with the coexistence, in the eight central nervous areas explored, of high and low affinity binding sites for PACAP-27 (Kd of 0.2 nM and 3.0 nM, respectively), and of only one class of binding sites for PACAP-38 (PACAP (1-38), Kd 0.2-0.9 nM). VIP inhibited only partially the binding of [125I]PACAP-27, and PHI, GRF(1-29)NH2 and secretin were ineffective at 1 microM. Chemical [125I]PACAP-27 cross-linking revealed a single specific 64 kDa protein species. In rat brain cortical membranes, saturation and competition experiments, using [125I]PACAP-38 as radioligand, indicated the presence of both high (Kd 0.13 nM) and low (Kd 8-10 nM) affinity binding sites for PACAP-38 and of low affinity (Kd 30 nM) binding sites for PACAP-27. These data taken collectively suggest the coexistence of PACAP-A receptors with a slight preference for PACAP-27 over PACAP-38 and of PACAP-B receptors that recognize PACAP-38 with a high affinity and PACAP-27 with low affinity. Both PACAP-27 and PACAP-38 stimulated adenylate cyclase with similar potency and efficacy. VIP was markedly less potent in this respect and also less efficient, except on cerebellar membranes.
...
PMID:Properties and distribution of receptors for pituitary adenylate cyclase activating peptide (PACAP) in rat brain and spinal cord. 166 4

Vasoactive intestinal peptide (VIP) receptors coupled to activation of adenylate cyclase have been previously identified in seminal vesicle membranes of rat. In the present study we demonstrate that the synthetic peptides [4-Cl-D-Phe6,Leu17]VIP and the growth hormone releasing factor (GRF) analog [Ac-Tyr1,D-Phe2]GRF1-29-NH2 inhibit in a competitive manner the specific 125I-VIP binding to the same membrane preparation. The order of potency of the two peptides compared to VIP was: VIP (IC50 = 1.3 +/- 0.5 nM) greater than [4-Cl-D-Phe6,Leu17]VIP(IC50 = 1600 +/- 45.0 nM) greater than [Ac-Tyr1,D-Phe2]GRF1-29-NH2(IC50 = 290.0 +/- 59.4 nM). Whereas VIP showed a stimulatory activity upon adenylate cyclase with a potency (ED50 = 7.0 +/- 0.7 nM) compatible with the affinity of the VIP binding sites previously described, the other two peptides tested showed no effect at that level. The behavior as antagonists of both [4-Cl-D-Phe6,Leu17]VIP and [Ac-Tyr1,D-Phe2]GRF1-29-NH2 was confirmed by: (a) the parallel shifts of the VIP dose-response curves for stimulation of adenylate cyclase activity in the presence of the antagonists; (b) the close agreement between the binding affinity and the inhibition of adenylate cyclase activity for the two peptides; and (c) the lack of effect of the two antagonists upon the adenylate cyclase activity stimulated by the beta-adrenoceptor agonist isoproterenol which indicates the specificity of the interaction.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Vasoactive intestinal peptide receptor antagonists in rat seminal vesicle membranes. 166 44

The osteoblast-like cells, UMR 106-01, express PTH receptors that are coupled to adenylate cyclase. Recently, we reported the isolation of a UMR 106-01 subclone, UMR 4-7, that is stably transfected with a Zn(++)-inducible mutant of the regulatory subunit of protein kinase A. Incubation of UMR 4-7 cells with Zn++ renders the cells unresponsive to cAMP agonists. This subclone, therefore, seemed particularly suitable for studies of PTH receptor regulation. In UMR 106-01 cells, PTH receptors are strikingly down-regulated by pretreatment with 8-Br-cAMP or 3-isobutyl-1-methylxanthine for 2 days. In UMR 4-7 cells, this effect is totally prevented by prior and concurrent treatment with Zn++. Zn++ addition to UMR 106 cells does not modify these responses. Treatment with the PTH agonist [Nle8,18,Tyr34]bovine PTH(1-34)NH2 [(NlePTH(1-34)] also markedly down-regulates PTH receptors in UMR 106 cells, but this effect is only partially inhibited in Zn(++)-induced UMR 4-7 cells. At high doses, the PTH antagonist, [Nle8,18,Tyr34]bovine PTH(3-34)NH2 [NlePTH(3-34)] also (partially) reduces PTH receptor availability. Receptor regulation by NlePTH(3-34) is not blocked in the cAMP-resistant cells, however. Coincubation of submaximal doses of NlePTH(1-34) (1 nM) with NlePTH(3-34) (1 microM) reduces receptor availability more than when the cells are exposed to either ligand alone. This decrease is only partially inhibited in Zn(++)-induced UMR 4-7 cells. In contrast to its additive effect on receptor regulation, NlePTH(3-34) efficiently competes for binding to the PTH receptor in UMR 106-01 cells and antagonizes the stimulatory effects of NlePTH(1-34) on both intracellular cAMP accumulation and gene expression driven by a transiently transfected synthetic cAMP-responsive enhancer. In conclusion, homologous down-regulation of PTH receptors is mediated by activation of both cAMP-dependent (via protein kinase A) and cAMP-independent pathways. PTH activates both pathways, whereas the effect of NlePTH(3-34) appears to be exclusively cAMP-independent. These results give new insights into mechanisms of PTH receptor regulation.
...
PMID:Cyclic adenosine 3',5'-monophosphate (cAMP)-dependent and cAMP-independent regulation of parathyroid hormone receptors on UMR 106-01 osteoblastic osteosarcoma cells. 171 28

Pituitary adenylate cyclase activating peptide (PACAP) tested as PACAP-(1-38)NH2 and PACAP-(1-27)NH2 and vasoactive intestinal polypeptide (VIP) were compared for their capacity to discriminate between high- and low-affinity VIP-preferring receptors that coexist in rat liver plasma membranes. This capacity was evaluated by the ability to 1) inhibit 125I-labeled-PACAP-(1-27)NH2, 125I-labeled-VIP, and 125I-labeled-helodermin binding and 2) to activate adenylate cyclase. PACAP-(1-27)NH2 bound specifically and reversibly to three classes of binding sites, as revealed by analysis of binding curves. On high-affinity VIP receptors (tested specifically by [125I]-helodermin binding), PACAP-(1-38)NH2 showed lower affinity than PACAP-(1-27)NH2 and VIP itself. On low-affinity VIP receptors, PACAP-(1-27)NH2 and -(1-38)NH2 showed similar modest affinity that was slightly higher however than that of VIP. For a third specific class of PACAP receptors (20% of PACAP receptors not recognized by VIP), PACAP-(1-38)NH2 showed higher affinity than PACAP-(1-27)NH2. Both PACAPs stimulated rat liver adenylate cyclase with the same low efficacy as VIP but with an affinity even greater [half-maximal effective concentration (EC50) 0.02 nM] than that of VIP (EC50 0.05 nM).
...
PMID:PACAP and VIP receptors in rat liver membranes. 184 75

HPLC-purified 125I-labeled vasoactive intestinal peptide (VIP) bound in a specific, saturable, and reversible manner to pancreatic plasma membranes isolated from newborn calves, from milk-fed calves at 28 and 119 days, and from weaned calves at 119 days. A series of VIP analogues, including pituitary adenylate cyclase-activating polypeptide (PACAP), displaced 125I-VIP binding and activated adenylate cyclase in the same order of relative potency: PACAP-38 greater than helodermin greater than VIP, PACAP-27 greater than PHM (human peptide with NH2-terminal histidine and COOH-terminal methionine amide). At maximally effective concentrations, these five peptides produced the same two- to threefold increase of adenylate cyclase activity in pancreatic membranes from newborn and 28-day-old calves, and fourfold in ruminant or preruminant animals at 119 days. The activation constant for PACAP-38 ranged from 0.1 to 0.34 nM throughout the postnatal development. Helospectin I and II were three times less potent than VIP in inhibiting 125I-VIP binding. At concentrations up to 0.1 microM, secretin, rat and human growth hormone-releasing factors, glucagon, oxyntomodulin, the truncated form of glucagon-like peptide-1 lacking the 6 NH2-terminal amino acid sequence (TGLP-1), GLP-2, gastric inhibitory peptide, gastrin, CCK, and insulin had no effect on binding. Scatchard plots from 28- and 119-day-old calves were compatible with the presence of two classes of 125I-VIP binding sites: one with a high affinity for VIP and a low binding capacity (Kd = 0.11-0.4 nM, Bmax = 66-174 fmol/mg protein) and the other with a low affinity and high binding capacity. At birth, only one class of binding sites was observed (Kd = 0.4 nM, Bmax = 858 fmol/mg protein). The covalently cross-linked PACAP-preferring 125I-VIP binding site is a glycoprotein of 55 kDa with higher sensitivity to PACAP vs. helodermin and VIP. Our results suggest that calf pancreatic functions might be regulated at an early stage of postnatal development by PACAP receptors linked to cAMP generation.
...
PMID:Characterization of binding sites for VIP-related peptides and activation of adenylate cyclase in developing pancreas. 184 91

Ovine granulosa cells respond, through transcriptional mechanisms, to preovulatory concentrations of gonadotrophins by secreting an Mr 30,000 polypeptide. To determine the stages of the oestrous cycle at which this polypeptide is secreted, corpora lutea were collected on Days 3, 7, 10, 13 and 16 (Day 0 = oestrus; n = 4 per group), cut into 1-mm slices, and incubated for 6-7 h with [35S]methionine. Radiolabelled polypeptides of intra- and extra-cellular origin were separated by polyacrylamide gel electrophoresis and quantitated by densitometry. The Mr 30,000 polypeptide was secreted at all stages of the luteal phase tested (Days 3-16), and represented approximately 24% of the total labelled polypeptide present in the medium; polypeptides of approximate Mr 14,000, 25,000 and 46,000 accounted for most of the other secreted proteins. Neither pituitary hormones (LH, FSH, prolactin) nor cholera toxin (chosen to activate adenylate cyclase) affected the rate of production of Mr 30,000 polypeptide, indicating that, once secretion has been initiated in the granulosa cells, it is not readily modulated by hormonal intervention after luteinization. Incubation of luteinized granulosa cells with tunicamycin (inhibits N-linked glycosylation reactions) showed that the secreted polypeptide consists of a heavily glycosylated amino acid backbone of approximately Mr 20,000. Western blot analysis established further that the polypeptide was not an inhibin subunit. However, NH2-terminal amino acid sequencing of the first 25 amino acids revealed a 68% sequence identity between the secreted polypeptide (Mr 30,000) and a human tissue inhibitor of metalloproteinases.
...
PMID:Secretion of a putative metalloproteinase inhibitor by ovine granulosa cells and luteal tissue. 184 78

Parathyroid hormone (PTH) and PTH-related proteins (PTHrP) interact with a common receptor in rat bone cells and in canine renal membranes with similar affinity, but PTHrP are substantially less potent than PTH in stimulating adenylate cyclase in canine renal membranes; in contrast, PTH and PTHrP are equipotent in stimulating adenylate cyclase in rat bone cells. This discrepancy has been largely viewed as reflecting differences in the relative efficiency of signal transduction of PTHrP between bone and kidney assay systems. To test the alternative (but not mutually exclusive) hypothesis that these differences could reflect interspecies differences in PTH receptors, we have characterized the bioactivity of amino-terminal PTHrP and PTH in rat and human renal cortical membranes (RCM) and compared them to results we previously reported in canine RCM. The stability of PTH and PTHrP peptides under binding and adenylate cyclase assay conditions was greater than 80% for each species. Competitive inhibition of [125I](Tyr36)hPTHrP-(1-36)NH2 binding to rat RCM by bPTH-(1-34) and (Tyr36)hPTHrP-(1-36)NH2 yielded nearly identical binding dissociation constants (3.7 and 3.6 nM, respectively), and binding to human RCM demonstrated slightly greater potency for PTHrP (0.5 nM) than for PTH (0.9 nM). Similarly, adenylate cyclase stimulating activity was equivalent for the two peptides in rat RCM, but PTHrP was twofold more potent than PTH in human RCM. Covalent photoaffinity labeling of protease-protected rat RCM yielded an apparent 80 kD receptor protein, and cross-linking of human RCM labeled an 85 kD receptor, indistinguishable in size from the canine renal PTH receptor. We conclude that rat, canine, and human renal cortical PTH receptors exhibit species specificity. The previously observed differences between rat bone cells and canine renal membranes in the efficiency of signal transduction by PTHrP may be explained, at least in part, by these species differences.
...
PMID:Interspecies comparison of renal cortical receptors for parathyroid hormone and parathyroid hormone-related protein. 185 88

Two monobiotinylated analogs of neuropeptide Y (NPY) were synthesized by coupling the N-hydroxysuccinimidyl esters of biotin and (6-biotinylamido)-hexanoic acid, respectively, to the free alpha-NH2 group of the side chain protected NPY peptide resin. Crude peptides obtained by HF cleavage were purified by RPLC and their integrities were confirmed by amino acid and mass spectral analysis. As with NPY, both biotinylated analogs inhibited 125I-NPY binding and adenylate cyclase activity of rat cardiac ventricular membranes in a dose-dependent manner. N-alpha-[(6-biotinylamido)-hexanoyl]-NPY exhibited potencies comparable to that of NPY whereas N-alpha-biotinyl-NPY was slightly less potent. In the in vivo experiments, however, both the biotinylated analogs exhibited responses comparable to NPY in increasing arterial blood pressure and decreasing heart rate in anesthetized rats. The responses of the biotinyl analogs were longer lasting than those of NPY. Histochemical studies revealed that N-alpha-[(6-biotinylamido)-hexanoyl]-NPY could label the NPY receptors in rat cardiac ventricular tissues. This labeling was specific since intact NPY inhibited the staining. These studies show that biotinyl-NPY analogs exhibit biological potencies comparable to intact NPY and can therefore be used to further probe the NPY-receptor interaction.
...
PMID:N-alpha-biotinylated-neuropeptide Y analogs: syntheses, cardiovascular properties, and application to cardiac NPY receptor visualization. 196 29

This study tests the hypothesis that atrial natriuretic factor (ANF) and C-ANF(4-23)-NH2 (C-ANF) augment cGMP generation and inhibit both cAMP generation and depolarization-induced catecholamine release in nerve growth factor treated pheochromocytoma cells by a pertussis toxin (PTX)-sensitive mechanism. Synthetic rat ANF(99-126) and the clearance receptor antagonist C-ANF (10(-12)-10(-9) M) inhibited basal and 5 microM vasoactive intestinal peptide (VIP)-induced cAMP generation in a concentration-dependent manner. These actions of ANF and C-ANF were blocked by 12-18 h pretreatment with PTX (100 ng/ml), suggesting ANF receptor coupling to adenylate cyclase via an inhibitory guanine nucleotide-binding protein. Both ANF (10(-11)-10(-9) M) and C-ANF (10(-11)-10(-8) M) also inhibited K(+)-induced catecholamine release in a concentration-dependent manner. ANF (10(-11)-10(-8) M) increased cGMP generation in a concentration-dependent manner but C-ANF did not. The accumulation of cGMP in response to ANF was not altered by treatment with PTX. Therefore, PTX dissociated the increased concentrations of cGMP from the ANF-mediated depression of evoked catecholamine release. C-ANF also dissociated elevations in cGMP concentrations from an ANF-mediated attenuation of evoked catecholamine release. The results of this study indicate that ANF inhibits adrenergic neurotransmission independent of guanylate cyclase.
...
PMID:Neuromodulatory effects of atrial natriuretic factor are independent of guanylate cyclase in adrenergic neuronal pheochromocytoma cells. 197 29


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---