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Biomedical subjects

C Biondi

Publications and source records attributed to C Biondi.

At least 55 records · Page 3Linked to original sources

Adenylyl cyclase activity and glucose release from the liver of the European eel, Anguilla anguilla.

The properties of adenylyl cyclase (AC) in liver membranes of the European eel (Anguilla anguilla) and the involvement of cAMP in glucose release from isolated hepatocytes in response to catecholamines were studied. Basal enzyme activity seemed essentially unaffected by GTP, while a biphasic response to increasing nucleotide concentrations was obtained in the presence of epinephrine. Eel liver AC was dose-dependently stimulated by guanosine 5'-O-(3-thiotriphosphate) and inhibited by guanosine 5'-O-(2-thiodiphosphate). AC activity, intracellular cAMP levels, and glucose release from isolated hepatocytes were significantly enhanced by NaF, forskolin, epinephrine, and phenylephrine. The rise in cAMP production stimulated by catecholamines was counteracted by propranolol, but not by phentolamine. Catecholamine-induced glucose output was instead partially antagonized by both phentolamine and propranolol. Complete inhibition was obtained only by the simultaneous presence of the two adrenergic antagonists. Glucose release from the cells was induced by dibutyryl cAMP and by the calcium ionophore ionomycin. In summary, these data provide the first characterization of eel liver AC system and suggest a direct role for cAMP in the catecholamine-dependent glucose output. Furthermore, the involvement of calcium ions in this cellular response is hypothesized.

Adenylyl Cyclases↗

Two for-Met-Leu-Phe-OMe analogues trigger selective neutrophil responses. A differential effect on cytosolic free Ca2+.

For-Thp-Leu-Ain-OMe and for-Met-delta(z)Leu-Phe-OMe are two conformationally restricted fMLP-OMe analogues able to discriminate between different biological responses of human neutrophils. In this paper, we demonstrate that the former peptide, which evokes only chemotaxis, does not alter human neutrophil Ca2+ levels. In contrast, for-Met-delta(z)Leu-Phe-OMe, which induces superoxide anion release and degranulation but not chemotaxis, significantly increases the cation concentration. The chelation of Ca2+ in both extracellular and intracellular media abolishes O2- production triggered by for-Met-delta(z)Leu-Phe-OMe, while the same procedure does not affect neutrophil chemotaxis towards for-Thp-Leu-Ain-OMe. We therefore suggest that chemotaxis, unlike superoxide anion release, is independent of Ca2+ enhancement in human neutrophils.

Calcium↗

MDL 12330A inhibits the non-neuronal adenylyl cyclase from the freshwater snail Planorbarius corneus, but the neuronal enzyme is activated by this compound.

N-(Cis-2-phenyl-cyclopentyl)azacyclotridecan-2-imine-hydrochloride (MDL 12330A), considered an inhibitor of adenylyl cyclase, has been tested on the enzyme activity of neuronal and non-neuronal tissues from the freshwater snail Planorbarius corneus. The drug dose-dependently activates the basal as well as agonist-stimulated adenylyl cyclase in the ganglionic preparations, while it exerts an inhibitory effect on the enzyme present in the non-nervous tissues examined. SQ 22536 and forskolin, respectively an inhibitor and activator of adenylyl cyclase, behave as generally reported both in central and peripheral tissues of the snail. This is, to our knowledge, the first report of a stimulatory action of MDL 12330A on an adenylyl cyclase system.

Adenylyl Cyclases↗

Effect of serotonin and neuropeptides on adenylate cyclase of the central nervous system and peripheral organs of the freshwater snail Planorbarius corneus.

The effect of serotonin, FMRFamide and the small cardioactive peptide B (SCPB) on adenylate cyclase activity of the central nervous system and some peripheral organs of the freshwater snail Planorbarius corneus was investigated. The amine and the cardioactive peptide stimulated the enzyme, although with different potencies, in all tissues studied and, when tested in combination, an additive activation was obtained. FMRFamide induced differential effects in the various targets: marked stimulation of adenylate cyclase, additive to that provoked by serotonin or SCPB, in salivary glands; inhibition of the enzyme, both alone and in combination with the other neuromediators, in the nervous tissue; whereas no influence was found in adenylate cyclase activity in the buccal mass. In the last of these tissues, the peptide might act through an intracellular second messenger other than cyclic AMP. The responsiveness of adenylate cyclase to these neuromediators in all the central ganglia suggested that they can exert an important role as neurotransmitters and/or neuromodulators in the central nervous system of the snail. Moreover, in the light of the differential sensitivity of adenylate cyclase in the salivary glands and buccal mass, we suggest that serotonin, FMRFamide and SCPB modulate the feeding behaviour of P. corneus in a complex way.

Adenylyl Cyclases↗

Effect of cyclic AMP level reduction on human neutrophil responses to formylated peptides.

The increase in human neutrophil cyclic adenosine monophosphate (cAMP) levels evoked by formylated peptides is significantly reduced in the presence of MDL 12330A, SQ 22536, GDPssS and clonidine, which inhibit the adenylyl cyclase system by acting at different sites in this enzyme complex. A similar effect is exerted by adenosine deaminase and dipyridamole, which alter the extracellular adenosine concentration. Neutrophil preincubation with adenylyl cyclase inhibitors or dipyridamole reduces chemotaxis and superoxide anion production triggered by peptides; adenosine deaminase, on the contrary, has no effect on neutrophil responses. Our results seem to indicate that: (1) the peptide-induced increase in neutrophil cAMP is due mainly to an action on the adenylyl cyclase system; (2) an enhancement of this cyclic nucleotide, even slight and necessarily transient, is required for chemotaxis and O2 production induced in neutrophils by formylated peptides; and (3) cAMP does not represent the crucial second messenger for adenosine in the modulation of neutrophil responses.

Adenosine↗

Effects of Ca2+ and calmodulin on adenylyl cyclase activity in sheep olfactory epithelium.

Sheep olfactory epithelium contains an adenylyl cyclase which is stimulated by many but not all odorants. Here we report that this enzyme is activated by calmodulin in a dose-dependent manner, and that calcium ions are required for this response. Odorant stimulation of adenylyl cyclase is unaffected by the complex Ca2+/calmodulin, as suggested by the results obtained both in Ca2+/calmodulin-depleted membranes and under calmodulin antagonist treatment; this confirms the prediction that the Ca2+ binding protein and odorants stimulate the olfactory adenylyl cyclase through parallel mechanisms. The persistent activation of the regulatory component of adenylyl cyclase by GppNHp does not alter the response of the enzyme to either odorant or Ca2+/calmodulin. In sheep olfactory epithelium a cAMP-phosphodiesterase activity is also present, which is highly inhibited by IBMX and aminophylline, scarcely by RO 20-1724, and unaffected by Ca2+/calmodulin. The modulatory role exerted by calcium on cAMP system in sheep olfactory signal transduction is discussed.

3',5'-Cyclic-AMP Phosphodiesterases↗

Olfactory transduction mechanisms in sheep.

The enzyme adenylyl cyclase from sheep olfactory epithelium is dually regulated by GTP and is highly sensitive to the nucleotide analogues GTP gamma S and GppNHp, as well as to fluoride ions and forskolin. Many, but not all, odorants tested are able to stimulate adenylyl cyclase in a dose-dependent manner and with different potencies. Such an effect is detectable only in the presence of GTP. The odorants belonging to the putrid class are the least effective in stimulating adenylyl cyclase activity, and only furfuryl mercaptan significantly increases cAMP biosynthesis. Mixtures of two odorants, chosen among those able to activate adenylyl cyclase, induce additive or supra-additive effects, suggesting the presence of many different receptor types. The presence of an alternative olfactory signal transduction process, i.e. the inositol phospholipid second messenger system, has been evaluated. Triethylamine, a putrid odorant completely ineffective on cAMP levels, is able to significantly increase inositol phosphate accumulation, indicating the coexistence of both cAMP- and InsP3-mediated signalling pathways in sheep olfactory epithelium.

Adenylyl Cyclases↗

Adenylate cyclase activity from Hirudo medicinalis segmental ganglia: modulation by calcium and calmodulin.

An adenylate cyclase activity stimulated by serotonin and calmodulin is present in the segmental ganglia of the leech Hirudo medicinalis. Removal of the endogenous calcium binding protein does not alter the responsiveness of the enzyme to serotonin. The calmodulin antagonist, trifluoperazine, drastically reduces the amine stimulatory effect on both intact and calmodulin-depleted membranes. We suggest that calmodulin-sensitive and serotonin-stimulated adenylate cyclase are, at least functionally, independent.

Adenylyl Cyclases↗

The controversial role of cAMP on amnionic prostaglandin release: effect of adenylate cyclase inhibition.

The suggested role of cAMP in the regulation of amnionic prostaglandin release was investigated using two adenylate cyclase inhibitors, MDL 12330A and SQ 22536. These substances exhibited a dose-dependent inhibitory effect on both amnionic enzyme and cAMP levels, but they did not influence prostaglandin E (PGE) release. In addition forskolin and IBMX (3-isobutyl-1-methylxanthine), two drugs known to increase cAMP levels, did not affect PGE output, while dibutyryl cyclic cAMP showed a dose-dependent inhibitory effect. On the basis of our data, the suggested role of amnionic adenylate cyclase in triggering prostaglandin release is not confirmed, and the pathway of phospholipase A2 activation at the onset of labor remains to be elucidated.

1-Methyl-3-isobutylxanthine↗

Adenylate cyclase activity from Hirudo medicinalis segmental ganglia: modulation by temperature and Mg2+ ions.

The basal, serotonin- and fluoride-stimulated activities of homogenate preparations from Hirudo medicinalis segmental ganglia increase with incubation temperature, reaching a maximum at 35 degrees C. Both basal and fluoride-stimulated activities yield linear Arrhenius plots, whereas serotonin-enhanced activity shows a break at 25 degrees C. Increasing Mg2+ concentrations stimulate the adenylate cyclase both in the absence and in the presence of serotonin. The affinity of the enzymatic system for the cation is unaffected by the amine.

Adenylyl Cyclases↗

Epidermal growth factor stimulation of lecithin release by human amnion.

Lecithin release from human amnion disks was assayed in basal conditions as well as under epidermal growth factor administration. The tissue responded to the peptide by increasing the phospholipid release. A significant effect was observed only after 30 min of treatment. A possible role of epidermal growth factor-induced amniotic lecithin release in fetal lung maturation as well as in the mechanism of delivery is discussed.

Amnion↗

Modulation of amnionic adenylate cyclase and cAMP phosphodiesterase by prostaglandins E1 and F2 alpha.

The action of prostaglandins E1 and F2 alpha on adenylate cyclase and cAMP phosphodiesterase was assayed in cell membrane fractions of amnion obtained before and after labor from term physiological pregnancies. Both prostaglandins stimulate the activity of adenylate cyclase in a dose-dependent manner. After spontaneous delivery both prostaglandins stimulate the activity of phosphodiesterase at lower doses and inhibit it at higher ones while the stimulatory effect of low doses is missing before labor. Such a behavior could represent a mechanism for the preservation of the cAMP-mediated processes throughout the entire event of delivery.

3',5'-Cyclic-AMP Phosphodiesterases↗

Effects of the small cardioactive peptide B (SCPB) on adenylate cyclase of the central nervous system and peripheral organs of the freshwater snail Planorbarius corneus.

The effect of the small cardioactive peptide B (SCPB) on adenylate cyclase activity of the central nervous system (CNS) and some peripheral organs of the freshwater snail Planorbarius corneus was investigated. This peptide stimulates enzyme activity in a dose-dependent manner in all the tested ganglia, in the salivary glands, the buccal mass and the oesophagus. The amount required for half-maximal stimulation is approx 0.1 microM. Moreover, the response of adenylate cyclase to SCPB progressively increases with time, without desensitizing. On the other hand, the peptide is ineffective on heart adenylate cyclase. The responsiveness of adenylate cyclase activity to the peptide and the wide distribution of SCPB-related immunoreactivity in all the tested ganglia suggest that this substance may exert an important role as neurotransmitter as well as neuromodulator in the CNS of the snail. Since SCPB is consistently present in the buccal and cerebral ganglia, associated nerves, salivary glands, buccal mass and oesophagus, and in the light of the appreciable effects exerted by SCPB on adenylate cyclase activity in the examined peripheral tissues, we suggest that the peptide is strongly involved in the control of feeding behaviour of P. corneus.

Adenylyl Cyclases↗