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Biomedical subjects

S Nicosia

Publications and source records attributed to S Nicosia.

At least 91 records · Page 5Linked to original sources
PubMed1985

Prostacyclin-lipoprotein interactions. Studies on human platelet aggregation and adenylate cyclase.

The in vitro effects of different lipoprotein fractions (VLDL, LDL and HDL) on human washed platelet aggregation, induced by collagen and thrombin, were evaluated in the presence and absence of PGI2. Although VLDL and LDL increased the platelet aggregation while HDL showed an opposite effect, none of the tested lipoprotein fractions affected the potency of PGI2 as inhibitor of platelet aggregation (IC50). In addition, studies were performed to evaluate the effects of lipoproteins on adenylate cyclase activity in human platelet membranes. The three lipoprotein classes inhibited both basal and PGI2-stimulated adenylate cyclase without affecting the EC50 for PGI2. This inhibitory activity was not specifically elicited by any protein or lipid since neither bovine serum albumin nor a lipid emulsion (Intralipid) displayed any inhibition. The effect on adenylate cyclase elicited by VLDL, LDL and HDL does not seem to be correlated with the activity on platelet aggregation. It is concluded that mediators other than cAMP might be involved in the control of platelet function by lipoproteins.

Adenylyl Cyclases↗
PubMed1985

Evaluation of novel compounds interacting with H2-histamine receptors: effect on histamine-sensitive adenylate cyclase activity in guinea-pig gastric mucosa.

The activity of a number of compounds belonging to the novel class of N-imidazolylphenyl-N'-alkyl-formamidines on histamine-sensitive adenylate cyclase was evaluated. All substances inhibited histamine-dependent adenylate cyclase activation. The compounds which were investigated in a wider concentration range, i.e. DA 4360, DA 4577, and DA 4626, behaved as simple competitive antagonists, yielding apparent KB values comparable with those estimated in conventional H2-receptor assays. These results provide further evidence for the highly selective H2-receptor antagonism of these new molecules, and confirm the suitability of the histamine-stimulated adenylate cyclase assay in guinea-pig gastric cells as a functionally reduced system for the study of H2 antagonists.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Differential effects of in vitro ethanol on prostaglandin E1-sensitive adenylate cyclase from smooth muscle cells and platelets.

In membranes of smooth muscle cells cultured from rabbit mesenteric artery, ethanol dose-dependently activates adenylate cyclase, both basal and PGE1- or GPP(NH)P-sensitive. The alcohol increases the maximal stimulation induced by PGE1 and GPP(NH)P, without greatly affecting their potency. The arrhenius plot displays a discontinuity point, which is only slightly lowered by ethanol. On the contrary, in membranes from human platelets ethanol inhibits basal, GPP(NH)P- and PGE1-sensitive adenylate cyclase, without modification of the prostaglandin or guanine nucleotide potency. The break point present in the Arrhenius plots is definitely lowered by the alcohol. In addition, ethanol decreases the thermostability of the enzyme. Neither in myocytes nor in platelets does ethanol affect the activation energy of the reaction. The data suggest that ethanol probably interacts directly with the membrane proteins, and that its effect is not mediated only through a perturbation of membrane lipid fluidity.

Adenylyl Cyclases↗
PubMed1984

6-Keto-prostaglandin E1-sensitive adenylate cyclase and binding sites in membranes from platelets and cultured smooth muscle cells.

6-keto-PGE1 elicits the same biological effects as PGI2 in human platelets and in rabbit aorta and mesenteric artery, being, however, less potent. We report here that 6-keto-PGE1 dose-dependently stimulates adenylate cyclase activity in membranes of human platelets and cultured myocytes from rabbit aorta and mesenteric artery. The extent of stimulation of the enzyme by 6-keto-PGE1 is the same as elicited by PGI2, while the apparent affinity is lower than that of prostacyclin, both in platelets and in vascular smooth muscle cells. At the level of platelet membranes, 6-keto-PGE1 interacts with the binding sites labelled by PGI2. However, in platelets as well as in mesenteric artery myocytes, 6-keto-PGE1 interacts with only one class of sites as demonstrated either by binding or by adenylate cyclase studies, whereas PGI2 in the same conditions recognizes two different classes.

Adenylyl Cyclases↗
PubMed1984

Prostacyclin-sensitive adenylate cyclase in cultured myocytes: differences between rabbit aorta and mesenteric artery.

Prostacyclin relaxes isolated strips of rabbit mesenteric artery and stimulates cholesteryl ester hydrolysis in rabbit aortic smooth muscle cells. Both effects are considered to be mediated by an increase in intracellular cAMP levels. Here we report that prostacyclin, prostaglandin E1 and two stable analogues of prostacyclin (5,6-dihydroprostacyclin and carbacyclin) dose dependently stimulate adenylate cyclase activity in membranes of cultured myocytes from both rabbit aorta and mesenteric artery. The rank order of potency in both systems was prostacyclin greater than carbacyclin greater than prostaglandin E1 greater than 5,6-dihydroprostacyclin, which parallels the order of potency observed for the vasodilator actions. Three other prostanoids, with limited vasoactive properties, prostaglandin D2, BW245C and 6-keto-prostaglandin F1 alpha failed to stimulate significantly adenylate cyclase activity. The two cell types differ in that the enzyme activation in aortic cell involves the interaction of each prostaglandin with one component of the adenylate cyclase system, while in mesenteric arterial cells the activation is brought about by the interaction with a higher and a lower affinity class of components.

Adenylyl Cyclases↗
PubMed1984

The use of stable prostaglandins to investigate prostacyclin (PGI2)-binding sites and PGI2-sensitive adenylate cyclase in human platelet membranes.

Prostacyclin, (PGI2) is a potent but unstable inhibitor of platelet aggregation, probably acting through stimulation of adenylate cyclase. A stable analogue of prostacyclin with antiaggregatory properties, 5,6-dihydro-PGI2 (6 beta-PGI1), and PGE1 can compete for the binding sites labelled by 3H-PGI2 in human platelet membranes (the affinity being PGI2 greater than PGE1 greater than 6 beta-PGI1). Both 6 beta-PGI1 and PGE1, as well as PGI2, bind to two classes of binding sites. 6 beta-PGI1 and PGE1 activate adenylate cyclase to the same extent as PGI2, with a rank order of potency which parallels that observed in binding experiments. The stimulation of this enzyme is brought about by interaction of each of these prostanoids with two different classes of components. The comparison of binding and adenylate cyclase data suggests that the sites to which PGI2, 6 beta-PGI1 and PGE1 bind might be coupled to the activation of adenylate cyclase. Since 6 beta-PGI1 seems to act through the same molecular mechanisms as PGI2, because of its stability it is an useful tool to investigate the mode of action of prostacyclin in platelets.

Adenylyl Cyclases↗
PubMed1984

Binding sites for 3H-LTC4 in membranes from guinea pig ileal longitudinal muscle.

Leutriene (LTC4) is one of the components of Slow Reacting Substance of Anaphylaxis (SRS-A) and is a potent constrictor of guinea pig ilea. The contraction is likely to be a receptor-mediated process. Here we report the existence of specific binding sites for 3H-LTC4 in a crude membrane preparation from guinea pig ileal longitudinal muscle. At 4 degrees C in the presence of 20 mM Serine-borate, binding increases linearly with protein concentration, reaches equilibrium in 10 minutes, and is reversible upon addition of 3 x 10(-5) M unlabelled LTC4. The dissociation curve is consistent with the existence of more than one class of binding site. Ca++ and Mg++ greatly enhance the binding of 3H-LTC4 at equilibrium. In the presence of 5 mM CaCl2 and MgCl2 not only LTC4 (IC50 10(-7)M), but also LTD4 (albeit with much lower affinity, IC50 = 6 x 10(-5) M) and the SRS-A antagonist FPL 55712 (IC50 = 10(-5) M) can compete with 3H-LTC4 for its binding sites. FPL 55712 only displaces 60-70% of the total amount bound, while LTC4 displaces 90-95%. These studies indicate that multiple classes of binding sites exist for 3H-LTC4 in guinea pig ileal longitudinal muscle, and that at least part of these binding sites might be related to the ability of LTC4 to contract guinea pig ilea.

Animals↗
PubMed1983

Effects of PGI2 on platelet aggregation and adenylate cyclase activity in human type IIa hypercholesterolemia.

The sensitivity to PGI2 of platelets of 20 selected type IIa hypercholesterolemic patients was studied and compared to that of platelets of 14 normocholesterolemic subjects. Type IIa subjects required higher concentrations of PGI2 to inhibit platelet aggregation elicited by 1 microM ADP, 1 microgram/ml collagen and 1.4 microM epinephrine. Adenylate cyclase activity was also measured in washed platelet membranes from the two groups of subjects. Adenylate cyclase activity, both basal and PGI2-stimulated, was not statistically different in the two groups examined. Therefore changes at the level of PGI2 receptors coupled to adenylate cyclase are not likely to be responsible for the different platelet sensitivity to prostacyclin.

Adenylyl Cyclases↗
PubMed1983

Properties of cytosolic proteins that confer vasoactive intestinal polypeptide-sensitivity to rat brain adenylate cyclase.

Rat brain cortex, caudate nucleus and cerebellum contain one or more factors that confer Vasoactive Intestinal Polypeptide (VIP)-, dopamine (DA)- and norepinephrine (NE)-sensitivity to adenylate cyclase in the absence of added GTP. These factors also stimulate the basal activity of the enzyme. The activity is found in a 100 000 X g supernatant; has an apparent molecular weight greater than 450 000 daltons; is inactivated by pronase, alkaline phosphatase and ammonium sulphate, and partially degraded by trypsin; and is stable to heat and acidic treatment. The effect of the factors is additive with that of guanosine-5'-triphosphate (GTP), and is not abolished by guanosine 5'-0-(2-thiodiphosphate) (GDP-beta-S). These results suggest that stimulation of adenylate cyclase by VIP, and most likely by DA and NE, can be modulated by soluble proteins.

Adenylyl Cyclases↗
PubMed1982

VIP stimulates ACTH release and adenylate cyclase in human ACTH-secreting pituitary adenomas.

The effect of vasoactive intestinal polypeptide (VIP) on in vitro ACTH release and adenylate cyclase activity was investigated in human ACTH-secreting pituitary adenomas from 4 patients with Cushing's disease and 2 patients with Nelson's syndrome. In all the tumors tested, VIP elicited a dose-dependent stimulation of hormone release from adenoma fragments (90-247% at 10-7 M VIP) and of cAMP formation in membrane preparations (75-140% at 3 X 10-6 M VIP). Therefore a role of VIP in the control of ACTH secretion in human ACTH-secreting adenomas is suggested; a cAMP-dependent mechanism of action can also be hypothesized.

Adenoma↗
PubMed1982

New pharmacological aspects on the antiasthmatic activity of tiaramide-HCl.

Tiaramide hydrochloride (THC) is a benzothiazoline derivative with a remarkable antianaphylactic activity: in anaesthetized guinea-pig it shows protecting effects against histamine (H)- and bradykinin (Bk)-induced bronchoconstriction, preventing increase of lung resistance and decrease of dynamic compliance. At the same time THC inhibits formation of circulating thromboxane A2 brought about by H and Bk. THC is also able to antagonize the contractions induced by CaCl2 on isolated guinea-pig tracheal spirals and its mode of action seems to be of the competitive type. Furthermore THC abolishes the "tonic" phase of K+-induced contractions of guinea-pig taenia coli which are dependent on inward movement of calcium, whereas the "phasic" component of the contractions is left unaltered. THC is a very weak inhibitor of 3'-5' cyclic adenosine monophosphate phosphodiesterase which is affected only at very high dosage (10(-2) M). The calcium antagonistic activity of THC may explain both its bronchodilating and antianaphylactic properties.

Anaphylaxis↗
PubMed1981

Effect of serum lipoproteins on the adenylate cyclase activity of rat liver plasma membranes.

Four rat lipoprotein classes [lymph chylomicrons, VLD (very-low-density), LD (low-density) and HD (high-density) lipoproteins] were tested for their ability to affect basal adenylate cyclase (EC 4.6.1.1) activity of rat liver plasma membranes. All the lipoproteins, with the exception of lymph chylomicrons, effectively increase the enzyme activity. VLD lipoproteins are the most active class (67% maximal increase), followed by HD lipoproteins (33%) and LD lipoproteins (23%). The effect of VLD lipoproteins is additive to that elicited by GTP or GTP plus glucagon (at least within a certain concentration range). VLD lipoproteins affect only the Vmax. of the enzyme, not the Km.

Adenylyl Cyclases↗