Biomedical subjects

F Picatoste

Publications and source records attributed to F Picatoste.

31 records · Page 2Linked to original sources

PubMed1988

Histamine H1-receptors mediate phosphoinositide hydrolysis in astrocyte-enriched primary cultures.

Astrocyte-enriched primary cultures of newborn rat brain hemispheres, prelabeled with [3H]inositol, accumulated [3H]inositol phosphate but not [3H]inositol bis- and tris-phosphate, after exposure to histamine for 60 min in the presence of 10 mM LiCl. The response to histamine was not a function of contaminating meningeal fibroblasts since no accumulation of [3H]inositol phosphate was elicited by histamine in meningeal cultures. The stimulation of phosphoinositide hydrolysis by histamine in astrocytes was dose-dependent (EC50 = 1.7 microM, maximal effect = 345% over basal levels) and was mimicked by several H1-receptor agonists. The use of selective receptor antagonists confirmed that the histamine response was the result of activation of H1-receptors. The histamine-induced [3H]inositol phosphate accumulation was completely abolished by omission of Ca2+ from the incubation medium. Astrocyte membranes specifically bound the radiolabeled H1-antagonist, [3H]mepyramine with an affinity (Kd = 5.9 nM) and a density of binding sites (Bmax = 113 fmol/mg protein) similar to rat brain. These results demonstrate the presence of functional histamine H1-receptors in rat brain astrocytes and suggest a role for histamine as a neuromodulator of astrocyte function.

Animals↗

PubMed1987

Histamine-stimulated phosphoinositide hydrolysis in developing rat brain.

Histamine stimulation of phosphoinositide breakdown has been studied in brain cortex from developing rats by measuring the accumulation of [3H]inositol monophosphate in lithium-treated slices prelabeled with [3H]inositol. Histamine stimulated phosphoinositide hydrolysis as early as day 3 after birth. The maximal response increased about 3-fold up to day 15 and remained essentially at the same level until adulthood. This developmental pattern contrasted with the 8-fold increase in [3H]mepyramine binding to histamine H1 receptors which takes place from the first to the end of the fourth week of life. Nonlinear regression analysis of concentration-effect curves for histamine generated at 6, 10, and 15 days of age revealed the presence of two components in the response, whereas a single component was found in adults. A high potency component showed EC50 values increasing from 6.4 microM at day 6 to 26.5 microM at day 15, and its contribution to the maximal response augmented from 65.8% to 78.9% during the same period. In 6-day-old animals, the H1 receptor agonists N alpha-methylhistamine and N alpha,N alpha-dimethylhistamine produced single-component responses with maximal effects similar to that estimated for the high potency component for histamine, and their relative potencies were consistent with an H1 receptor-mediated response. Inhibition constants for mepyramine, calculated from the parallel displacement of the concentration-response curves for N alpha-methylhistamine and the high potency component for histamine (6.3 nM and 10.8 nM, respectively) closely agreed with the reported affinity of rat brain H1 receptors for this compound. The low potency component of the response (EC50 = 175 microM at day 6 and EC50 = 260 microM at day 15) did not involve histamine-H2, serotonin 5-HT2, alpha 1-adrenergic, or muscarinic receptors. Pretreatment of 6-day-old cortical slices with the irreversible antagonist phenoxybenzamine, at concentrations that completely abolish [3H]mepyramine binding, left about 25% of the response to 1 mM histamine unaffected. This portion of the response, which was, moreover, insensitive to 1 microM mepyramine, was of a magnitude similar to that of the low potency component. Thus, at early stages of rat brain development, histamine induces phosphoinositide hydrolysis in part through a mechanism different from activation of H1 receptors. The loss of histamine potency and efficacy at H1 receptors throughout development is discussed and the natural occurrence of H1 receptor subsensitivity suggested.

Aging↗

PubMed1986

Phosphoinositide hydrolysis mediated by histamine H1-receptors in rat brain cortex.

Histamine stimulated the accumulation of [3H]inositol 1-phosphate in the presence of lithium in [3H]inositol-prelabelled slices from rat brain cortex in a concentration-dependent manner, with an EC50 value of 94.7 microM. High concentrations of antagonists of histamine H2 receptors, muscarinic receptors, alpha 1-adrenoceptors and serotonin receptors did not inhibit the effect. The histamine H1-receptor antagonists mepyramine, triprolidine, promethazine, d-chlorpheniramine and the tricyclic antidepressant doxepin inhibited the response with Ki values corresponding to an interaction with histamine H1-receptors. The EC50 for the response was about three times lower than the Ki value (approximately 300 microM) for the inhibition by histamine of [3H]mepyramine binding to membranes from rat brain cortex. Partial inactivation of H1-receptors with the alkylating antagonist phenoxybenzamine resulted in similar reductions in [3H]mepyramine binding sites and in the maximal histamine-induced [3H]inositol 1-phosphate accumulation, without affecting the KD for the radioligand or the EC50 for the response. The apparent dissociation constant for histamine calculated from these experiments (KA = 92.2 microM) was not different from the EC50 value. The present results indicate that histamine-stimulated phosphoinositide hydrolysis in rat brain cortex is mediated by H1-receptors and that no receptor reserve is present.

Animals↗

PubMed1986

[3H]mepyramine binding to histamine H1 receptors in bovine retina.

The promethazine-sensitive [3H]mepyramine binding was used to determine the presence of histamine H1 receptors in membranes from bovine retina. Specific mepyramine binding to retinal membranes was reversible, saturable and of high affinity. The apparent dissociation constant (KD = 2.2 +/- 0.4 nM) and the density of binding sites (Bmax = 60.9 +/- 5.1 fmol/mg protein), obtained in equilibrium studies, were similar to those found in bovine brain cortex. Binding was stereospecific and the inhibitory potencies of H1 and H2 antagonists indicated that [3H] mepyramine binding sites in the retina have characteristics of H1 receptors.

Aminopyridines↗

PubMed1979