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Results for “Second Messenger Systems”

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At least 199 records · Page 11Linked to original sources
PubMed1987

Multiple types of neurotransmitter binding sites in the rat neuroblastoma B 50 cell line. II. Response of second messenger systems to physiological stimuli in proliferating and differentiated cells.

The functionality of the alpha 1-, beta-adrenergic and muscarinic cholinergic binding sites of neuroblastoma B 50 is investigated under proliferating and differentiating conditions. In proliferating cells, the stimulation of the alpha 1-adrenergic and muscarinic cholinergic binding sites by their respective agonists causes an increase in both extracellular calcium association with the cells and phosphatidylinositol (PI) turnover; effects usually associated with functional receptors. When the cells are induced to differentiate morphologically with dibutyryl cyclic AMP (db-cAMP), extracellular calcium or a combination of both, the activity of the muscarinic receptor-coupled PI turnover is strictly correlated with the binding affinity of the receptor. This is not the case for the alpha 1-adrenergic receptor stimulation of PI turnover. The latter result, however, may be explained in terms of the intrinsic properties of the inducing agents used to cause neurite extension. The stimulation of the beta-adrenergic binding site with isoproterenol in proliferating cells, both with and without a phosphodiesterase inhibitor present, does not result in cellular cAMP accumulation. In morphologically differentiated cells, only the db-cAMP-induced state exhibits an increase in [3H]adenosine incorporation into cellular cAMP upon isoproterenol stimulation. This happens only in the presence of a phosphodiesterase inhibitor. The data presented in this study are discussed in terms of the affinity of the receptors for their respective ligands and in terms of the intrinsic properties of the inducing agents.

Adenylyl Cyclases↗
PubMed1986

Go, a guanine nucleotide-binding protein: immunohistochemical localization in rat brain resembles distribution of second messenger systems.

We have localized a guanine nucleotide-binding protein, Go, in rat brain by immunohistochemistry with a selective polyclonal antiserum to the alpha 39 subunit of Go. Specific staining is widely distributed, abundant in neuropil, absent from neuronal cell bodies, and displays regional heterogeneity. Staining is enriched in cerebral cortex, particularly the molecular layer, neuropil of the hippocampal formation, striatum, substantia nigra pars reticulata, molecular layer of the cerebellum, substantia gelatinosa of the spinal cord, and posterior pituitary. High density staining in the substantia nigra reflects a Go-containing striatonigral pathway since striatal lesions reduce ipsilateral immunostaining in the pars reticulata. Confirming immunostaining, quantitative [32P]ADP-ribosylation of nigral membranes with pertussis toxin indicates a 66% +/- 11% (mean +/- SEM) reduction of Go ipsilateral to striatal lesions. Go may be associated with Purkinje cells in the cerebellum since membranes from mutant mice (Nervous), which postnatally lose Purkinje cells, are markedly depleted in pertussis toxin substrate. The localizations of Go correspond in many areas with those of protein kinase C, a component of the phosphatidylinositol cycle, suggesting a major role for Go in the brain related to regulation of the phosphatidylinositol cycle.

Adenosine Diphosphate Ribose↗
PubMed2004

Dopamine deficits and regulation of the cAMP second messenger system in brains of simian immunodeficiency virus-infected rhesus monkeys.

The basal ganglia, structures rich in the neurotransmitter dopamine, are primarily affected during human immunodeficiency virus (HIV) infection. The authors measured levels of dopamine and its metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, in brains of uninfected and simian immunodeficiency virus (SIV)-infected rhesus monkeys during the asymptomatic stage of the infection. Moreover, the authors investigated changes in cyclic adenosine monophosphate (cAMP) and cAMP response element-binding protein (CREB), two factors involved in the signaling pathway of dopamine. The brain regions examined were the nucleus accumbens and the corpus amygdaloideum, which are limbic structures of the basal ganglia that are involved in the pathophysiology of psychiatric disorders and substance abuse. Dopamine content was reduced in both regions of SIV-infected monkeys compared to uninfected animals. Moreover, dopamine deficits were associated with a decrease in expression of total CREB. Intracellular concentrations of cAMP were decreased in nucleus accumbens and remained unchanged in corpus amygdaloideum of SIV-infected macaques. Changes in dopamine signaling were not related to pathology or viral load of the investigated animals. The results suggest that dopamine defects precede neurologic deficits and implicate dysfunction of the dopaminergic system in the etiopathogenesis of HIV dementia. Therefore, affective complications in HIV subjects should not be interpreted only as reactive psychological changes. The alterations in the mesolimbic dopaminergic system during asymptomatic stage of SIV infection implicate a biological background for psychiatric disorders in HIV infection.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Effects of LH and an LH-releasing hormone agonist on different second messenger systems in the regulation of steroidogenesis in isolated rat Leydig cells.

The stimulation of steroid production in Leydig cells by LH is accompanied by increased cyclic AMP levels, activation of protein kinase A, increased phosphorylation of at least six phosphoproteins and requires protein synthesis. However, an LH-releasing hormone agonist (LHRH-A) can stimulate steroid production without stimulation of cyclic AMP levels. In the present study we have shown that LH action involves calcium fluxes through the plasma membrane, in addition to activation of protein kinase A. The action of LHRH-A, in contrast, does not require calcium fluxes and is not potentiated by 1-methyl-3-isobutylxanthine, indicating that cyclic AMP is not involved. Extracellular calcium is required for the action of both LH and LHRH-A. An increase in intracellular calcium concentration due to the effect of ionophore A23187 did not stimulate steroidogenesis and had deleterious effects on intracellular adenosinetriphosphate levels. LH and 4 beta-phorbol-12-myristate-13-acetate (PMA), an activator of protein kinase C, both stimulated phosphorylation of proteins of 17 000 and 33 000 mol. wt, whereas LHRH-A had no effect. However, compared with the effect of LH, PMA had a much smaller effect on steroid production, indicating that even if protein kinase C may be activated by LH its role in the regulation of steroid production may be less important than the role of protein kinase A. Action of LHRH-A does not appear to be mediated by calcium fluxes, protein kinase C activation or active protein phosphorylation.

Animals↗
PubMed2002

Signaling networks in the pathophysiology and treatment of mood disorders.

Over the past decade, the focus of research into the pathophysiology of mood disorders (bipolar disorder and unipolar depression in particular) has shifted from an interest in the biogenic amines to an emphasis on second messenger systems within cells. Second messenger systems rely on cell membrane receptors to relay information from the extracellular environment to the interior of the cell. Within the cell, this information is processed and altered, eventually to the point where gene and protein expression patterns are changed. There is a preponderance of evidence implicating second messenger systems and their primary contact with the extracellular environment, G proteins, in the pathophysiology of mood disorders. After an introduction to G proteins and second messenger pathways, this review focuses on the evidence implicating G proteins and two second messenger systems-the adenylate cyclase (cyclic adenosine monophosphate, cAMP) and phosphoinositide (protein kinase C, PKC) intracellular signaling cascades-in the pathophysiology and treatment of bipolar disorder and unipolar depression. Emerging evidence implicates changes in cellular resiliency, neuroplasticity and additional cellular pathways in the pathophysiology of mood disorders. The systems discussed within this review have been implicated in neuroplastic processes and in modulation of many other cellular pathways, making them likely candidates for mediators of these findings.

Adenylyl Cyclases↗
PubMed1993

Effects of chronic lithium and carbamazepine treatment on G-protein subunit expression in rat cerebral cortex.

Although lithium and carbamazepine (CBZ) are effective in the treatment of bipolar affective disorder, their mechanism of action is still unknown. Recent evidence suggests that lithium and CBZ might exert their therapeutic effects by modulating the function of guanosine triphosphate (GTP)-regulatory (G) proteins associated with central nervous system second messenger systems. In the present study, we showed that chronic lithium administration decreases G alpha s, G alpha i1, and G alpha i2 messenger RNA (mRNA) abundance by 25%-30% in rat cerebral cortex. However, the levels of G alpha s, G alpha i1, and G alpha i2 mRNA were unaffected by chronic CBZ treatment. The effects of lithium on G alpha s, G alpha i1, and G alpha i2 mRNA levels appear to be selective, as the mRNA levels of G alpha o, G alpha x, G beta 1, G beta 2, and G beta 3 subunits remained unchanged. Two days after terminating chronic lithium treatment, changes in G alpha s, G alpha i1, and G alpha i2 mRNA levels were not demonstrable. Short-term administration of lithium (2 days), however, reduced only the G alpha i2 mRNA levels. Surprisingly, there was no significant difference in the amount of immunologically detectable G alpha s-s, G alpha s-1, G alpha i(1 + 2), G alpha 0, and G beta (1 + 2) in the cortex of rats chronically treated with lithium or CBZ, compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

A multifunctional calmodulin-stimulated phosphatase.

This review summarizes current knowledge concerning structure-function, substrate specificity, localization, and regulatory properties of calcineurin. Calcineurin is composed of two nonidentical subunits, one of which is responsible for catalytic activity and calmodulin binding while the other subunit contains four high-affinity Ca2+-binding sites. The enzyme possesses calmodulin-stimulated and metal ion-dependent phosphatase activity toward several nonprotein and phosphoseryl-, phosphothreonyl- and phosphotyrosyl-containing protein substrates. These recent results suggest that the protein may play a multifunctional role in interactions between the Ca2+/CaM second messenger system and other second messenger systems.

Animals↗
PubMed1991

Histamine receptors and interactions between second messenger transduction systems.

Histamine H1- and H2-receptors have been classically associated with two distinct intracellular second messenger systems. H2-receptors are coupled via a Gs regulatory protein to adenylate cyclase and stimulate cyclic AMP formation, while H1-receptors mediate many of their effects via the products of inositol phospholipid hydrolysis. It is becoming clear, however, that there is a substantial 'cross-talk' between these intracellular second messenger systems in a number of tissues. In guinea-pig cerebral cortical slices, H1-receptor stimulation can augment the direct cyclic AMP responses to adenosine or H2-receptor stimulation via a mechanism which appears to involve both products of inositol phospholipid hydrolysis, inositol triphosphate and diacylglycerol. In contrast, a reverse interaction can occur in bovine tracheal smooth muscle and agents which raise intracellular cyclic AMP levels can inhibit H1-receptor-mediated inositol phospholipid hydrolysis. In addition to these interactions between cyclic AMP and phosphoinositide signalling systems, the H1-receptor-mediated inositol phospholipid response in mammalian cerebral cortex can be regulated (both positively and negatively) via mechanisms which do not involve changes in cyclic AMP levels.

Animals↗