Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A short review of the role of cyclic nucleotides and prostaglandins (PGs) in normal and pathological functions of the heart is given. Possible interrelationships of these two regulatory systems have been studied by using spontaneously beating rat atria preparations. Addition of noradrenaline (NA) to the incubate (1 . 10(-6) M) caused an increase in amplitude and frequency which was preceded and parallelled by an elevation of the tissue cAMP level. A transient increase in cGMP and PGE values was also seen. Propranolol (5 . 10(-6) M) abolished the increase in amplitude and frequency as well as in cAMP and PGE concentrations. Indomethacin (1 . 10(-5) M) inhibited the formation of PGE. The increase in cGMP was blocked by phenoxybenzamine. Interchange between beta- and alpha-receptors according as the temperature is lowered has been described earlier. Hypothermia (20 degrees C) had a positive inotropic effect on the atria and increased the tissue cAMP concentration. Loading of the atria caused an increase in cAMP without any effects on cGMP or PGs. Slight hypoxia did not change the cAMP or PG levels, but elevated the cGMP values. Arrhythmias induced by hypo- or hyperpotassemia did not modify the biochemical parameters measured. PGF2alpha (1. 10(-5) M) normalized the atrial rhythm and increased the amplitude without changing cyclic nucleotide or PG levels. PGE1 (1 . 10(-4) M) increased the amplitude of normorhythmic atria and the tissue concentration of cAMP. PGE2 was the only PG tested which stimulated the heart adenylate cyclase in vitro. There seems to be close but complicated relationships between cyclic nucleotides and PGs in the heart.
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PMID:The role of cyclic nucleotides and prostaglandins in heart function. 21 11

Hormonal modulation of neurotransmission emerged as a concept from the recognition that adrenocortical steroids exert profound effects at the level of receptors, G-proteins and effector units. G-proteins, a family of guanine nucleotide binding regulatory components that couple neurotransmitter receptors to various types of intracellular effector systems, appear to be a key target of glucocorticoid (GC) action in the CNS. It is thought that Gs/Gi mediates stimulation/inhibition of adenylate cyclase (AC system), which forms cyclic AMP as second messenger, while receptors stimulating phospholipase C do so through Go to produce two second messengers, inositol 1,4,5-triphosphate and diacylglycerol (PI system). Recent evidence suggests that GC increase Gs alpha-and decrease Gi alpha-protein subunit expression without affecting Go alpha. Activation of central pre- and postsynaptic 5-HT1A receptors which are linked to the Gi-AC complex, induces hypothermia and ACTH/cortisol release in rodents and humans. Compared with controls, patients with a major depressive disorder exhibit increased basal cortisol secretion associated with decreased hypothermic and ACTH/cortisol responses. The attenuated neuroendocrine and thermoregulatory response to 5-HT1A receptor activation may reflect a GC-dependent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) system and subsensitivity of the presynaptic 5-HT1A-Gi-AC complex function. Differential regulation of 5-HT1A and 5-HT2 function leading to a relative 5-HT2-Go-PI complex supersensitivity may maintain HPA hyperactivity during the course of depression. These findings corroborate recent reports that GC, via GC-GC receptor (GR) complex activated promotion of gene transcription, modify the expression 5-HT1A-coupled Gi (but not 5-HT2-coupled Go) resulting in altered sensitivity of 5-HT1A-mediated signal transduction and further support the hypothesis of a differential regulation of 5-HT1A and 5-HT2 receptor function and a GC-GR/5-HT1A-G-protein--effector system-related abnormality in depression.
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PMID:The 5-HT receptor--G-protein--effector system complex in depression. I. Effect of glucocorticoids. 164 69

The cannabinoid receptor that has been pharmacologically characterized for hypothermia, spontaneous activity, analgesia and catalepsy in rodents is the same pharmacological receptor that inhibits adenylate cyclase in vitro. The inhibition of adenylate cyclase by the cannabinoid receptor results from an interaction with Gi, based on the biochemical kinetic properties of the response, the sensitivity to pertussis toxin ADP-ribosylation, and the thermodynamic characteristics of the response. From precedents based on studies of the well-characterized G protein coupled receptors, rhodopsin and the beta-adrenergic receptor, we can predict the tertiary structure of the cannabinoid receptor. Three sites of potential glycosylation are present on the receptor. However, treatment of N18TG2 neuroblastoma cells with tunicamycin to prevent glycosylation of newly synthesized receptors failed to alter cannabinoid-induced inhibition of cyclic AMP accumulation. The cannabinoid response was rapidly desensitized (within 1/2 h). Treatment of cells with tunicamycin failed to alter agonist-induced desensitization processes. These findings can be more veraciously interpreted as we gain a better understanding of the cellular dynamics of the cannabinoid receptor.
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PMID:The cannabinoid receptor: biochemical and cellular properties in neuroblastoma cells. 180 46

The behavioural and biochemical profile of the sigma ligand and putative antipsychotic agent, BMY 14802 (alpha-(4-fluorophenyl)-4-(5-fluoro-2- pyrimidinyl)-1-piperazine butanol) has been determined in the mouse and rat. In mice, pretreatment with BMY 14802 attenuated both amphetamine-induced hyperactivity and conditioned avoidance responding, consistent with its previously reported antipsychotic potential. In common with 5-HT1A receptor agonists or partial agonists, BMY 14802 induced (a) a dose-dependent hypothermia in mice; (b) aspects of the 5-HT behavioural syndrome in rats, (c) antagonised mescaline-induced head twitches in mice and (d) generalised to the 8-hydroxy-2-(di-n-propylamino)tetralin discriminative stimulus over the dose range of 3-15 mg/kg. BMY 14802 had appreciable affinity for the 5-HT1A receptor (pIC50 = 6.7 compared to 7.3 for sigma binding) and antagonised forskolin-stimulated adenylate cyclase activity with a pEC50 of 6.2, consistent with an agonist action at this receptor. The results support the involvement of 5-HT1A receptors, but not the sigma binding site, in the behavioural profile of BMY 14802.
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PMID:Behavioural and biochemical evidence of the interaction of the putative antipsychotic agent, BMY 14802 with the 5-HT1A receptor. 183 33

Adenosine exerts numerous effects in the central and autonomic nervous systems, most of which seem to be receptor mediated. Several studies have revealed two distinct receptors, based upon effects of adenosine on adenylate cyclase activity, designed A1 or A2 according to whether the cyclase is inhibited or activated. However, since not all adenosine receptors are linked to adenylate cyclase some authors base their classification on the rank orders of potencies of adenosine analogues in eliciting responses. The purine seems to function as a modulatory substance in the heart, blood, ileum, vas deferens, and adipose tissue. In addition, important responses to exogenously added adenosine are also induced in the bronchi, urinary bladder, taenia coli, parietal cells of the stomach and renin secretion. Adenosine and its analogues elicit anticonvulsant responses, sedation and hypothermia through their actions in the central nervous system. The mechanisms by which adenosine elicits its responses have not been clearly established. The activation of A1 receptors depresses the release of neurotransmitters and inhibit the influx of Ca into nerve terminals. Whether this effect is induced by interaction with Ca channels or by impairment of Ca dependent processes associated with neurotransmitter release is unknown. In the rat heart adenosine inhibits adenylate cyclase and subsequently the phosphorylation of L-type Ca channels, resulting in a decrease of calcium influx in the muscle cell. The responses to activation of A2 receptors in smooth muscle consist in relaxation presumptively by an increase of K current which would hyperpolarize the cell.
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PMID:[Adenosine: physiological and pharmacological actions]. 215 91

The effect of cooling of animals on phosphorylation of proteins in hypothalamus, pituitary gland and adrenals, was studied in white mice. The regulation of protein phosphorylation in cells during hypothermia was carried out via the adenylate cyclase system in all these structures. The calcium-calmodulin system took part in this process in hypothalamus and adrenals.
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PMID:[The regulation of protein phosphorylation in the hypothalamus, hypophysis and adrenals during deep hypothermia]. 217 87

We used an in vitro radioligand receptor binding assay with rat cerebral cortex, hippocampus and striatum membrane preparations to show that 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554) had much higher affinity for 5-HT1A recognition sites than for 5-HT1-non-A, 5-HT2, benzodiazepine, dopamine D-2 and alpha 2-adrenergic recognition sites. The compound inhibited the activity of forskolin-stimulated adenylate cyclase in rat hippocampal membranes. Intraperitoneal injection of BP-554 to mice decreased the concentration of only 5-hydroxy-indoleacetic acid of the amines and their metabolites in the brain and decreased the accumulation of 5-hydroxytryptophan in the brain after decarboxylase inhibition by 3-hydroxybenzylhydrazine. Furthermore, the administration of BP-554 caused hypothermia and increased serum corticosterone levels in mice. The observed effects of BP-554 were similar to those of 8-hydroxy-2-(di-n-propylamino)tetralin. These results suggest that BP-554 acts as a selective 5-HT1A receptor agonist in vivo.
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PMID:Agonist activity of a novel compound, 1-[3-(3,4-methylenedioxyphenoxy)propyl]-4-phenyl piperazine (BP-554), at central 5-HT1A receptors. 253 78

Ethanol prevents the decrease of the number of beta-adrenoceptors in the cerebral cortex induced by chronic treatment of rats with desipramine. The activation of the adenylate cyclase, the second messenger, by beta-adrenergic agonists is reduced somewhat less than after treatment with desipramine alone. The present paper examined the hypothesis that ethanol inhibits the neuronal adaptation to desipramine chronic treatment at the functional level as well. Desipramine reduced exploratory behavior (crossings, rearings) as did ethanol. Combined treatment attenuated the effect of desipramine. Cognitive performance was investigated using an active avoidance paradigm. Desipramine-treated rats did not learn the task in contrast to control animals. Again, combination treatment with ethanol improved the ability of the rats to perform the task. The activity of cerebral beta-adrenergic mechanisms was assessed by injection of salbutamol, a beta-adrenoceptor agonist in rats pretreated with 5-hydroxytryptophan (5-HTP). The augmentation of the 5-HTP-induced wet dog shake behavior by salbutamol was observed in all animals independent of the chronic treatment. However, rats treated with desipramine were less active than those treated with tap water or ethanol. The effect of desipramine in the presence of a high concentration of salbutamol was attenuated by ethanol. The observed increase of the number of wet dog shakes correlates with the function of these receptors. In two paradigms, spontaneous motility and apomorphine-induced hypothermia, ethanol did not affect the action of desipramine. It is noteworthy that desipramine acted in both situations within a short time period (minutes to hours). The findings strongly suggest that ethanol can prevent adaptive changes in the brain induced by chronic treatment with the antidepressant desipramine. This is of special interest since the adaptation of beta-adrenoceptors is thought to be critical for the antidepressant efficacy of various therapeutic interventions applied in psychiatric practice.
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PMID:Effects of desipramine on rat behavior are prevented by concomitant treatment with ethanol. 254 96

The effect of dopamine D-1 and D-2 receptor stimulation on body temperature has been investigated in male mice. The selective D-2 receptor agonists, quinpirole and LY 163502, and the mixed D-1/D-2 agonist, apomorphine, induced a dose-dependent hypothermia, whereas the selective D-1 receptor agonists, SK&F 81297, SK&F 38393 and SK&F 75670, induced hyperthermia. The hyperthermic responses of these agents were of a similar magnitude although the relative efficacies determined in vitro with the adenylate cyclase assay were different. The peripherally acting D-1 agonist, fenoldopam, did not influence body temperature, indicating that the hyperthermia is mediated, centrally. Studies with combinations of quinpirole and SK&F 38393 showed that the effect of one of the substances could be counteracted by the other. Furthermore, antagonist studies showed that the hypothermia induced by quinpirole could be inhibited by the D-2-selective antagonist, YM 09151-2, and by the mixed D-1/D-2 antagonist, cis(Z)-flupentixol, but not by the D-1-selective antagonist, SCH 23390. Similar results were found for apomorphine-induced hypothermia. SK&F 38393-induced hyperthermia could be antagonized by all three antagonists. These results suggest that the two receptor subtypes act differentially on body temperature, and that they influence a common out-put system, but in opposite directions. These findings are opposite to those of behavioural studies, where a synergistic function of D-1 and D-2 receptors has been demonstrated in the regulation of motor function.
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PMID:The effects of dopamine D-1 and D-2 receptor agonists on body temperature in male mice. 257 99

The antidepressant potential of rolipram and inhibitors of phosphodiesterase (PDE) which are selective for cyclic AMP has previously been ascribed to enhancement of central noradrenergic transmission by the combination of two mechanisms of action: increase of synthesis of noradrenaline and release (presynaptic component) and concomitant potentiation of noradrenaline signals due to inhibition of phosphodiesterase (postsynaptic component). To examine the contribution of the latter component to the antidepressant action, rolipram, ICI 63 197 or Ro 20-1724 were given to mice which were depleted of monoamines in the brain by combined pretreatment with reserpine, alpha-methyl-p-tyrosine and p-chlorophenylalanine. Rolipram, ICI 63 197 and Ro 20-1724 dose-dependently reversed the hypothermia and hypokinesia induced by this pretreatment. Imipramine and pargyline were inactive in this respect, indicating that their antidepressant effect depends on the availability of endogenous monoamines. The antihypothermic and antihypokinetic action of rolipram was not prevented by blockade of central beta-adrenergic or dopaminergic receptors. It is concluded that an action of rolipram, beyond postsynaptic receptors, essentially contributes to its antidepressant effect. The postsynaptic adenylate cyclase/cyclic AMP phosphodiesterase system is thought to be the most likely target. The unique properties of rolipram to stimulate both presynaptic and postsynaptic components of central neurotransmission should enable more efficient transduction of postsynaptic signals by circumventing presynaptic inhibitory feedback mechanisms, responsible for the delay in the therapeutic action of conventional antidepressant drugs.
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PMID:Rolipram, a novel antidepressant drug, reverses the hypothermia and hypokinesia of monoamine-depleted mice by an action beyond postsynaptic monoamine receptors. 294 76


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