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)

The ultrastructure of brain microvessels, their permeability to serum albumin, the activities of some endothelial enzymes and the effect of histamine were investigated in rats after a prolonged hypobaric-hypoxic treatment. After prolonged hypoxia, the permeation of serum albumin into endothelial cells increased together with the number of pinocytotic vesicles of the endothelium. Intracarotid histamine stimulated this process even further, and its effect was mediated by H2-histamine receptors. After hypoxia the specific activity of capillary alkaline phosphatase and gamma-glutamyl transpeptidase remained unchanged, while that of adenylate cyclase was greatly increased. Histamine did not modify the structure of tight junctions of isolated capillaries of normoxic animals. Both hypoxia- and histamine-induced modification of the brain microvessels were accompanied by an increase of pinocytosis, which may be stimulated by the activation of capillary adenylate cyclase.
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PMID:The blood-brain barrier in hypoxia: ultrastructural aspects and adenylate cyclase activity of brain capillaries. 647 24

A LH function test was used to assess the effect of a previously administered dose of ovine LH on the granulosa from the four largest preovulatory follicles, F1-F4, of laying hens. At intervals of 1, 3, and 6 hr after intravenous ovine LH (40 micrograms; a dose previously shown to cause atresia) or carrier solution (1% bovine serum albumin solution, BSA), a second dose of LH or carrier was injected. The progesterone contained in the dissected granulosa of the F1-F4 follicles 45 min after the second injection was measured by radioimmunoassay. With birds injected with BSA, the mean basal levels ranged from 17 to 59 ng progesterone per granulosa, irrespective of the follicular type. In short-term experiments, i.e., 45 min after LH, the mean progesterone contents of F1 (262 ng) and F2 (137 ng) were significantly higher than their controls, whereas those of F3 (59 ng) and F4 (21 ng) did not change. The response per cell was greater in the F1 granulosa than in that of F2-F4; other evidence is presented to support a hypothesis that the F1 granulosa contains a larger LH receptor population. The effect of LH over a longer period (6 hr) was shown by a decline in the steroidogenic response of the F1 granulosa only. The kinetics of this decline (estimated t1/2 13.7 hr) resembled that previously reported for adenylate cyclase activity in granulosa cells from postovulatory follicles (POF) (t1/2 about 14.4 hr).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of luteinizing hormone on progesterone production by the follicular granulosa in the ovarian hierarchy of the domestic fowl (Gallus domesticus). 665 36

The technique of fluorescence recovery after photobleaching was used to measure the lateral mobility of membrane integral proteins in reticulocyte plasma membranes which were treated to modify the 'fluid' lipid or immobilized protein fractions, hence increasing the relative prevalence of obstacles to protein lateral motion. This was achieved by either: (1) treating the plasma membranes with phospholipase A2 followed by extraction of the hydrolysis products using fatty-acid-free bovine serum albumin, resulting in a decrease in the membrane 'fluid' lipid portion; or (2) preincubating the plasma membranes with polylysines, resulting in plasma membrane protein aggregation and immobilization. As the prevalence of obstacles to lateral motion increased in plasma membranes through the treatments described above, the mobility of the membrane integral proteins diminished. Experimental results for the dependence of protein mobility on the prevalence of obstacles to lateral motion were compared to theoretical data in order to verify the applicability of the percolation theory to reticulocyte plasma membranes. The influence of a decrease in the 'fluid' lipid and an increase in the immobilized membrane protein fractions upon the hormone-stimulated adenylate cyclase activity has been studied as well. As the 'solid' lipid and immobilized membrane protein fractions decreased, both the hormone-stimulated adenylate cyclase activity and the fraction of beta-adrenergic receptors with high affinity to hormone diminished. It was shown that this correlation can be caused by a decrease in membrane fraction accessible to the movement of the interacting proteins of the adenylate cyclase complex. Hormonal stimulation of adenylate cyclase is discussed in terms of the percolation theory.
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PMID:Modification of fluid lipid and mobile protein fractions of reticulocyte plasma membranes affects agonist-stimulated adenylate cyclase. Application of the percolation theory. 779 48

Anterior pituitary cells cultured as three-dimensional cell aggregates and incubated with gonadotropin-releasing hormone (GnRH) show a biphasic pattern of luteinizing hormone (LH) release when steroid-free bovine follicle fluid is added to the culture medium. Initially, the GnRH-induced LH release is low (lag-phase response), but LH release increases during further incubations with GnRH (primed-state response). Also, in aggregates of dispersed cells from long-term ovariectomized rats cultured for 2 days in the presence of 1% bovine follicle fluid, a low initial LH responsiveness to GnRH could be restored. Cycloheximide was found to block the induction of the primed state, indicating the protein synthesis dependency of GnRH self-priming. In aggregates from gonadotroph-enriched cell populations obtained by velocity sedimentation in a bovine serum albumin gradient, addition of 1% bovine follicle fluid to the culture medium also restored a biphasic pattern of GnRH-induced LH release. However, co-culturing the gonadotroph-enriched cell aggregates with a folliculo-stellate (FS) cell-enriched population resulted in the attenuation of the differences in LH secretion rate between early and late responses to GnRH. The present example of the attenuation by folliculo-stellate cells of pituitary hormone secretion responses demonstrates that the cells regulate the cellular processes leading to a priming of the LH response to GnRH, rather than interfering with the access of GnRH to its receptor in gonadotrophs. Finally, it was found that stimulation of the adenylate cyclase enzyme with maximal effective doses of forskolin counteracted the inhibitory effect of bovine follicle fluid on the initial LH response to GnRH, but did not completely abolish the biphasic pattern of LH release. It is concluded that coupling to the adenylate cyclase enzyme is presumably involved in the LH surge inhibiting feedback action on the pituitary cells, but also other messenger pathways and intercellular interactions between pituitary cells may play a role in establishing a biphasic LH release at the pituitary level following GnRH administration.
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PMID:Influence of folliculo-stellate cells on biphasic luteinizing hormone secretion response to gonadotropin-releasing hormone in rat pituitary cell aggregates. 818 Jun 83

In common with many other animal cells in culture, BHK21, CHO and NIH-3T3 cells adopt bizarre stellate or arborized shapes when exposed, in the absence of serum, to agents which increase cytoplasmic cyclic AMP (cAMP). Dibutyryl cAMP, 3-isobutyl-1-methylxanthine, 5'-deoxy-5'-methylthioadenosine, cholera toxin and the invasive adenylate cyclase from Bordetella pertussis all induce similar shapes. Time lapse video recording of BHK21 cells spreading on fibronectin shows that stellate shapes are generated by outgrowth of neurite-like processes led by small fans of ruffling membrane. These structures stain strongly for F actin, and their outgrowth is completely inhibited by cytochalasin D. Thus if stellation is caused by microfilament depletion, this must be selective for subsets of microfilaments. We have quantified the shape changes of BHK21 cells using the parameter dispersion. They are prevented by low concentrations (1% by volume and below) of bovine sera. The inhibitory component of foetal bovine serum acts humorally, behaves as a macromolecule and is itself inhibited by suramin, but platelet-derived growth factor, insulin, vasopressin and bradykinin are inactive. The inhibitory activity of serum may be due to phospholipids, since it can be replaced by lysophosphatidic acid in the presence of serum albumin.
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PMID:Shapes of cells spreading on fibronectin: measurement of the stellation of BHK21 cells induced by raising cyclic AMP, and of its reversal by serum and lysophosphatidic acid. 838 76

Glucocorticoid receptor levels within a given cell determine the glucocorticoid effect in the target tissue. Glucocorticoid receptors are present in adrenal medullary cells in culture where they are involved in the regulation of catecholamine biosynthesis. Modulation of glucocorticoid receptor protein and/or messenger RNA levels in response to cyclic nucleotides has been found in various cell types. In this study, we have investigated the effects of cyclic AMP and cyclic GMP on glucocorticoid receptor binding and glucocorticoid receptor-mediated function in Percoll-isolated bovine adrenal medullary cells in culture. Four-day treatment of cells with 8-bromo-cyclic AMP (10(-3) M) an analogue of cAMP, or forskolin (10(-5) M), an activator of adenylate cyclase, decreased soluble [3H]dexamethasone binding by 55 and 54%, respectively. 8-Bromo-cyclic GMP treatment decreased [3H]dexamethasone binding by 31 and 34% at 10(-5) and 10(-4) M, respectively. Treatment with 8-bromo-cyclic AMP or forskolin, but not 8-bromo-cyclic GMP, elevated cortisol levels in the medium of treated cells, presumably by elevating steroidogenesis in contaminating cortical cells. Cultures further purified to produce chromaffin-enriched cell cultures, also showed a loss (41%) in soluble [3H]dexamethasone binding when treated with 8-bromo-cyclic AMP (10(-3) M). Four-day treatment of standard Percoll-isolated cells with low concentrations of cortisol (10(-9) to 2 x 10(-7) M) similar to that found in the medium of 8-bromo-cyclic AMP-treated cells, did not decrease soluble [3H]dexamethasone binding, whereas higher cortisol concentrations (10(-6) M) produced a 62% loss in soluble binding. Adsorption of cortisol with bovine serum albumin (5 mg/ml) prevented a cortisol (10(-6) M)-induced loss in soluble [3H]dexamethasone binding with no effect on the 8-bromo-cyclic AMP-induced loss in binding, suggesting that the decrease in binding observed following 8-bromo-cyclic AMP treatment is not due to the release of cortisol from contaminating cortical cells. Finally, we report a loss in the ability of 8-bromo-cyclic AMP- or 8-bromo-cyclic GMP-treated cells to fully induce the activity of phenylethanolamine N-methyltransferase in response to cortisol, indicating that decreases in soluble [3H]dexamethasone binding translate into a decrease in the functional consequence of glucocorticoid receptor binding in adrenal medullary cells. In conclusion, these results indicate that long-term increases in cyclic nucleotide second messengers are able to decrease glucocorticoid receptor binding in bovine adrenal medullary cells, via a mechanism independent of released cortisol.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Glucocorticoid receptors in bovine adrenal medullary cells in culture: regulation by cyclic nucleotides. 839 Jun 25

Boar spermatozoa loaded with the Ca2+ probe fluo-3 were incubated in various Tyrode's-based media similar to those used for in vitro fertilization (IVF), and samples were then analysed by two-colour flow cytometry; propidium iodide was included in the media to detect membrane-damaged ("dead") cells. If media contained bicarbonate/CO2 (a component thought to promote capacitation), part of the live sperm population experienced a considerable influx of Ca2+ into both head and tail compartments. The percentage of responding cells reached a maximum after about 30 min, but both during and after this period there was also a steady increase in the number of dead cells. This bicarbonate-mediated increase in cell death took place in the absence of external Ca2+. Evidence was obtained that the entry of propidium iodide was preceded by a change in permeability of the plasma membrane, detectable by leakage of carboxydichlorofluorescein, and it was therefore deduced that the Ca2+ influx detected by fluo-3 was due to destabilization of the plasma membrane. A similar response could be produced by both caffeine and papaverine (best known as phosphodiesterase inhibitors), but neither cyclic AMP nor activators of adenylate cyclase had any effect. There was no influence of substrate on the process, but, in comparison to poly(vinyl alcohol), serum albumin enhanced it. The precise relevance of this destabilization to capacitation is not yet clear, but it seems significant that the process is mediated or enhanced by components often specifically included in IVF media, and that different individual cells respond after different times.
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PMID:Flow cytometric studies of bicarbonate-mediated Ca2+ influx in boar sperm populations. 839 Dec 78

Phosphorylation of rap 1b in human platelets correlates with both an upward shift of the protein on sodium dodecyl sulfate polyacrylamide gels and the translocation of the phosphorylated protein to the cytosolic fraction of platelets. We reported that this phenomenon occurs in platelets in response to agents that stimulate adenylate cyclase and thereby activate the cyclic AMP-dependent protein kinase. We now have evidence that phosphorylation of rap1b in platelets is also induced by nitric oxide generating compounds through stimulation of guanylate cyclase and activation of the cyclic GMP-dependent protein kinase. We observed time-dependent phosphorylation of rap1b and dose-dependent inhibition of collagen-stimulated aggregation in washed platelets incubated with S-nitroso serum albumin. In the presence of a combination of iloprost and 3-morpholinosydnonimine, when both PKA and PKG are activated, phosphorylation of rap1b increased synergistically to a level three times higher than the sum of their individual actions.
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PMID:Nitric oxide stimulates the phosphorylation of rap1b in human platelets and acts synergistically with iloprost. 861 88

Pituitary adenylate cyclase-activating peptide (PACAP)-like immunoreactivity was demonstrated by immunocytochemistry together with calcitonin gene-related peptide (CGRP)-like immunoreactivity in small to medium-sized neurons in the trigeminal ganglion and in nerve fibers in the iris, ciliary body, cornea, choroid and sclera of the rabbit eye. The regional distribution of PACAP-27- and PACAP-38-like immunoreactivity in the eye was studied by radioimmunoassay: the highest concentrations were found in the iris sphincter and ciliary body. The distribution pattern resembled that of CGRP-like immunoreactivity, which is a well-known constituent of sensory C-fibre neurons. Intravitreal injection of PACAP-27 or PACAP-38 induced conjunctival hyperemia, swelling of the anterior segment of the eye, miosis and breakdown of the blood-aqueous barrier, manifested as a marked aqueous flare response. Tetrodotoxin pretreatment inhibited the conjunctival hyperemia, the swelling of the anterior segment of the eye, and the miosis but not the aqueous flare response. The concentration of PACAP-like immunoreactivity in the aqueous humor was increased greatly following infrared irradiation of the iris, topical application of formaldehyde to the cornea, or intravitreal injection of endotoxin or bovine serum albumin. Also the concentration of CGRP-like immunoreactivity in the aqueous humor was increased greatly. Both in vivo and in vitro studies showed that capsaicin caused a parallel release of PACAP-like immunoreactivity and CGRP-like immunoreactivity from the uvea. Injection of PACAP-27 and PACAP-38 resulted in the release of CGRP-like immunoreactivity (and PACAP-like immunoreactivity) into the aqueous humor and PACAP-27 and PACAP-38 were also found to evoke tachykinin-mediated contractions of the isolated iris sphincter muscle, indicating that PACAP induces positive feedback on C-fibres. Thus, PACAP is a sensory neuropeptide in the eye. Since the PACAP-induced ocular responses mimicked the symptoms of inflammation, and since the PACAP-like immunoreactivity concentration in the aqueous humor was greatly increased following noxious stimulation, we suggest that it takes part in the inflammatory responses of the rabbit eye.
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PMID:Distribution and effects of pituitary adenylate cyclase-activating peptide in the rabbit eye. 863 27

The report describes the results of a study the effect of pH and binding of six physiologically active compounds (isoproterenol, yohimbine, theophylline, propranolol, clonidine and carbachol) on the molecular structure of human serum albumin (HSA) using dynamic light scattering. It was found that the albumin globule had the most compact configuration (Stokes diameter 59-62A) at physiological pH 7.4. The changes in pH both increased to 8.0 and decreased to 5.4, resulting in the growth of globule size to 72-81A. At acidic shift of pH an additional peak arose in the correlation spectra. This peak was caused by the light scattering on the structures with the Stokes diameters of 29-37A, which conformed to the sizes of the albumin subdomains. The additional peak was not displayed at basic shift of pH. The interaction with propranolol, clonidine and carbachol, which hinder adenylate cyclase (AdC) signaling system of a cell, initiated structural rearrangements similar to acidic transitions. Isoproterenol, yohimbine and theophylline, which activate AdC, caused the conformational changes of HSA similar to basic transitions.
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PMID:The influence of pH alteration and pharmacological modulators of adenylate cyclase system on human serum albumin conformation. 974 99


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