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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Adenosine 3',5'-monophosphate (cAMP), its dibutyryl derivative (Db-cAMP) and other adenine nucleotides have been micro-injected into the hypothalamic region of the unanaesthetized cat and the effects on body temperature, and on behavioural and autonomic thermoregulatory activities observed. 2. Db-cAMP and cAMP both produced hypothermia when applied to the pre-optic anterior hypothalamus. With Db-cAMP the hypothermia was shown to be dose dependent between 50 and 500 mug (0-096-0-96 mumole). 3. AMP, ADP and ATP also produced hypothermia when injected into the pre-optic anterior hypothalamus. 4. The order of relative potencies of the adenine nucleotides with respect both to the hypothermia produced and to the autonomic thermoregulatory effects observed were similar. Db-cAMP was most potent and cAMP least. 5. Micro-injection into the pre-optic anterior hypothalamus of many substances including saline produced in most cats a non-specific rise in body temperature apparently the result of tissue damage. Intraperitoneal injection of 4-acetamidophenol (paracetamol 50 mg/kg) reduced or abolished this febrile response. 6. The hypothermic effect of the adenine nucleotides has been compared with the effects produced in these same cats by micro-injections of noradrenaline, 5-hydroxytryptamine, a mixture of acetylcholine and physostigmine (1:1), EDTA and excess Ca2+ ions. 7. It is concluded that as Db-cAMP and cAMP both produce hypothermia, it is unlikely that endogenous cAMP in the pre-optic anterior hypothalamus mediates the hyperthermic responses to pyrogens and prostaglandins.
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PMID:The effects of cyclic adenosine 3',5'-monophosphate and other adenine nucleotides on body temperature. 17 Mar 96

Right and left guinea-pig atria responded to decreasing temperatures (42-27 degrees C) with elevation for force of contraction and concomitant increases in cAMP. When atria were rapidly cooled from 42 to 27 degrees C the increase in cAMP occurred prior to the onset of the inotropic responses. Papaverine (3 X 10(-5) M) potentiated the effects of temperature on cAMP and force of contraction on left atria driven at 0.5 Hz. On right atria beating spontaneously at frequencies above 2 Hz papaverine only potentiated the effect of decreasing temperatures on the response of cAMP but not on that of force of contraction. Time course studies of the effects of isoprenaline (3 X 10(-8) M) on right atria at 27 degrees C showed large inotropic responses to isoprenaline which were accompanied by increases in cAMP. At 42 degrees C the responses of force of contraction and cAMP to isoprenaline occurred faster and were only short-lasting. As with the time courses for isoprenaline, dose-response curves for the effect of isoprenaline and papaverine on cAMP content and force of contraction also appeared to be shifted towards higher levels at hypothemia. However, pD2 values reflected increases in affinity for inotropic, but not for the cAMP responses to isoprenaline and papaverine at hypothermia. These results show that cyclic AMP is involved in the inotropic responses to hypothermia, but not in the supersensitivity of heart to isoprenaline and papaverine as observed at low temperatures.
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PMID:The role of cyclic AMP in temperature-dependent changes of contractile force and sensitivity ot isoprenaline and papaverine in guinea-pig atria. 20 21

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

The effects of the diterpene sclareol glycol (SG) of the labdane family on rectal body temperature in rats were studied. Sclareol glycol induced dose-dependent changes in temperature. At the lowest dose (5 mg/kg) SG produced a decrease followed by an increase in temperature; at the middle dose it produced a decrease and at the largest dose, an increase in rectal temperature. Sclareol glycol caused changes in apomorphine-induced hypothermia (at the low and middle doses it reversed hypothermia, and at the high dose hypothermia was enhanced). Sclareol glycol produced a dose-dependent reversal of reserpine-induced hypothermia. These results suggest that the diterpene sclareol glycol induces changes in core body temperature by interacting with dopamine (DA) receptors and with the second messenger system of 3',5'-AMP in the brain thermoregulatory areas.
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PMID:Effects of the diterpene sclareol glycol on body temperature in rats. 275 74

Chronic treatment of rats with imipramine or electroconvulsive shock evokes a significant decrease in binding of [3H]-clonidine to homogenates from the rat brain cerebral cortex. The decrease in binding is accompanied with a functional hyposensitivity of alpha 2-adrenoceptors as measured by attenuation of several central effects of clonidine (e.g. attenuation of clonidine-induced hypothermia, sedation, inhibition of noradrenaline formation). The influence of these antidepressants on alpha 2-adrenoceptors may be of importance in the context of data showing that prolonged treatment with these drugs attenuates the cAMP formation after noradrenergic stimulation, and that the alpha 2-adrenoceptors together with beta-adrenoceptors contribute to the formation of the second messenger. The prolonged administration of imipramine and electroshock, as well as other antidepressant treatments, e.g. administration of the monoamine oxidase inhibitor pargyline or atypical antidepressants such as trazodone, mianserin citalopram, fluoxetine, inhibit the interaction between beta- and-alpha-adrenoceptors (with the alpha 2-subtype playing a major role) and may thus contribute to the phenomenon known as the beta-adrenoceptor down-regulation. The inhibition of the interaction between alpha and beta-adrenoceptors by antidepressants may occur in multiple ways: 1. by lowering the number of beta-adrenoceptors; 2. by lowering the number of alpha 2-receptors (e.g. after imipramine or ETC); 3. by a shift of alpha 2 receptors to a higher affinity state, which represents a desensitized form of the receptor (e.g. decrease in Kd after imipramine or citalopram); 4. by a shift to an antagonist preferring state of the receptor (e.g. after treatment with fluoxetine or trazodone); 5. by a combination of the mentioned above. The functional interaction between alpha and beta adrenoceptors is presumably not dependent upon the integrity of the noradrenergic system, as it not only occurs but also is enhanced in reserpinized or 6OHDA treated rats.
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PMID:The role of alpha 2-adrenoceptors in the mechanism of action of antidepressant drugs. 284 26

Hypothermia has previously been demonstrated to induce supersensitivity (defined as a decrease in the ED50) of guinea pig left atria to the negative inotropic effect of carbachol. In the present investigation, the dissociation constant (pKA or -log KA) for carbachol, determined using benzilylcholine mustard, was found to be significantly increased at 25 degrees C compared to 37 degrees C. However, the increase in pD2 (-log ED50) for carbachol at 25 degrees C was much less than would be predicted from the increase in pKA. Increasing the extracellular Ca2+ concentration or the frequency of stimulation, both of which, like hypothermia, are believed to increase Ca2+ influx into cardiac cells, resulted in a decrease in sensitivity to carbachol. Carbachol had no significant effect on cAMP or cGMP levels at either 37 degrees C or at 25 degrees C. These results suggest that the hypothermia-induced increase in sensitivity of left atria to carbachol can be explained by an increase in the affinity of the muscarinic receptor for this agonist. However, the expression of this increased affinity appears to be limited. This may be due to a concurrent decrease in the efficacy of the carbachol muscarinic receptor complex.
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PMID:The mechanism of hypothermia-induced supersensitivity of guinea pig left atria to carbachol. 285 62

5'-Deoxy-5-iodotubercidin was previously reported to cause potent muscle relaxation and hypothermia when injected i.p. into mice. In normotensive rats, i.v. injection reduced blood pressure and heart rate. 5-Iodotubercidin possessed the same in vivo activities whereas tubercidin was pharmacologically almost inactive. None of these compounds interacted significantly with Al adenosine receptors, as determined by their ability to displace 3H-N6-phenylisopropyladenosine or 3H-5'-N-ethylcarboxamidoadenosine bound to rat brain membranes. Furthermore these compounds were much weaker than adenosine as agonists of adenosine-stimulated adenylate cyclase in guinea-pig brain slices (A2 receptors). A previous report showed that 5'-deoxy-5-iodotubercidin and 5-iodotubercidin were very potent inhibitors of adenosine kinase from rat or guinea-pig brain and were potent inhibitors of 3H-adenosine uptake into brain slices; relative to the halogenated derivatives, tubercidin was quite weak as an inhibitor of adenosine kinase and of adenosine uptake. We therefore propose that a significant part of the in vivo activity of the two halogenated tubercidin analogues may not be due to a direct agonist action at A1 and/or A2 adenosine sites (as proposed for a number of other metabolically-stable analogues of adenosine) but may result from an inhibition of reuptake of endogenously-released adenosine; the increased extracellular levels of adenosine resulting from this action could then interact directly with membrane receptors. Consistent with this, low concentrations of 5'-deoxy-5-iodotubercidin were shown to significantly potentiate the effects of exogenous adenosine on blood pressure and heart rate in anaesthetized rats and on adenosine-stimulated cAMP generation in guinea-pig brain slices. None of these compounds interacted with central benzodiazepine receptors. The cardiovascular and behavioural effects of 5'-deoxy-5-iodotubercidin and 5-iodotubercidin were blocked by theophylline; results from the cardiovascular studies suggest there may be different adenosine receptors in heart and blood vessels.
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PMID:Studies on several pyrrolo[2,3-d]pyrimidine analogues of adenosine which lack significant agonist activity at A1 and A2 receptors but have potent pharmacological activity in vivo. 301 53

Forskolin, a direct activator of the catalytic subunit of adenylate cyclase (AC), and the cyclic nucleotide analogs dibutyryl cAMP (dBcAMP), 8-bromo cAMP (8-BrcAMP) and dibutyryl cGMP (dBcGMP) were tested for their ability to reverse the hypothermia or hypokinesia of mice depleted of presynaptic endogenous monoamines by pretreatment with reserpine, alpha-methyl-p-tyrosine and p-chlorophenylalanine. Forskolin and the cAMP analogs decreased the rectal temperature and inhibited locomotor activity in normal mice. In mice depleted of brain monoamines forskolin reversed the hypothermia and hypokinesia; dBcAMP and 8-BrcAMP antagonized the hypothermia but were only marginally effective in reversing the hypokinesia. DBcGMP was inactive. The antihypothermic action of forskolin or salbutamol was enhanced by the novel antidepressant and cAMP selective phosphodiesterase inhibitor rolipram (4RS-[3-cyclopentyloxy-4-methoxy-phenyl]-2-pyrrolidone). As an indirect effect via release of endogenous monoamines stimulating postsynaptic receptors was precluded by the monoamine-depleting pretreatment, forskolin and the cAMP analogs are thought to exert their antidepressant action by directly increasing brain cAMP availability. This is achieved by forskolin via activation of the catalytic subunit of AC and by the cAMP analogs via substitution for cAMP. These findings suggest that antidepressant activity is crucially linked to enhanced cAMP availability within brain effector cells. The successful treatment of endogenously depressed patients with rolipram supports this assumption.
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PMID:Effects of forskolin and cyclic nucleotides in animal models predictive of antidepressant activity: interactions with rolipram. 302 33

The efficacy of the selective adenosine cyclic 3',5'-monophosphate (cAMP) phosphodiesterase (PDE) inhibitor (+/-)-rolipram and its optical isomers (0.006 to 25 mg kg-1) in inducing characteristic behavioural changes like hypothermia, hypoactivity, forepaw shaking, grooming and head twitches in rats has been examined. (+)-Rolipram was found some 15 times less potent than the racemate suggesting a stereoselective interaction with a rat brain cAMP phosphodiesterase isoenzyme. Following their intracerebral administration, the stereoisomers also demonstrated their unusual potency ratio. These findings suggested that (+)-rolipram is a less potent neurotropic PDE inhibitor in-vivo than its (-)-enantiomer.
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PMID:Neurotropic effects of the optical isomers of the selective adenosine cyclic 3',5'-monophosphate phosphodiesterase inhibitor rolipram in rats in-vivo. 613 85

The effect of the phosphodiesterase (PDE) inhibitors rolipram, Ro 20-1724 and isobutylmethylxanthine (IBMX) on motor behaviour and rectal temperature was studied in mice, rats and guinea pigs following intraperitoneal administration (0.39 to 25 mg/kg). The selective adenosine cyclic 3',5'-monophosphate (cAMP) PDE inhibitors rolipram and Ro 20-1724 in each species caused a dissimilar pattern of neurotropic effects: Hypothermia and hypokinesia in mice, hypothermia, hypokinesia and head twitches in rats, hypothermia, hyperkinesia and head twitches in guinea pigs. The head twitches were associated with forepaw shaking and increased grooming. Rolipram was the most potent compound in the three species. In guinea pigs it was less active than in rats or mice. Ro 20-1724 was approx. 15 to 30 times less potent in inducing the characteristic alterations in the various species. The alkylxanthine PDE inhibitor IBMX, 0.39 to 6.25 mg/kg, slightly stimulated the locomotor activity of mice and rats, most probably due to antagonism of central adenosine actions. IBMX, 6.25 to 25 mg/kg, caused a pattern of neurotropic effects identical to that produced by the selective cAMP PDE inhibitors, indicating the prevalence of the cAMP PDE inhibitory action over the adenosine antagonistic action at higher dosages. IBMX was approx. as potent as Ro 20-1724 in this respect. The species differences in the neurotropic responses to cAMP PDE inhibition in vivo presumably reflect similar differences in the extent of cAMP accumulation in brain tissue of the three species in vitro. Enhanced availability of brain cAMP in vivo in the various rodent species seems to be correlated with diverse patterns of more or less complex motor behavioural symptoms.
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PMID:Species differences in behavioural effects of rolipram and other adenosine cyclic 3H, 5H-monophosphate phosphodiesterase inhibitors. 619 Sep 91


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