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Biomedical subjects

C Kennedy

Publications and source records attributed to C Kennedy.

At least 253 records · Page 14Linked to original sources

ATP produces vasodilation via P1 purinoceptors and vasoconstriction via P2 purinoceptors in the isolated rabbit central ear artery.

P1 and P2 purinoceptors mediating mechanical responses in isolated rabbit ear artery were studied by comparing responses to adenosine triphosphate (ATP), alpha, beta-methylene ATP, and adenosine, both when endothelial cells were intact and when they had been removed by mechanical rubbing (as confirmed by histochemical staining and near abolition of relaxation to acetylcholine). alpha, beta-Methylene ATP and ATP (but not adenosine or acetylcholine) contracted preparations at resting tone. alpha, beta-Methylene ATP was significantly more potent as a contractile agent than ATP. Neither was significantly affected by removal of the endothelium. Acetylcholine, ATP, and adenosine relaxed arteries whose tone had been raised by 10(-6) M histamine. Removal of the endothelium virtually abolished relaxations to acetylcholine and significantly decreased those to adenosine and ATP. All relaxations to adenosine and ATP were significantly antagonised by 8-phenyltheophylline, a potent P1 purinoceptor antagonist. alpha, beta-Methylene ATP further contracted the high-tone preparation and was again unaffected by removal of the endothelium. These results confirm that endothelial cells can mediate vasodilation. They also show that adenosine (and ATP) can elicit vasodilation via P1 purinoceptors both on the endothelial cells and on the smooth muscle of the isolated rabbit central ear artery. P2 purinoceptors, however, appear to be located on the smooth muscle only and mediate vasoconstriction.

Adenosine Triphosphate↗

Metabolic and behavioral consequences of lidocaine-kindled seizures.

Daily administration of lidocaine results in progressive increases in frequency and duration of convulsions in response to a dose of drug which was previously subconvulsive--a pharmacological kindling phenomenon. The effects of such lidocaine-kindling on local cerebral glucose utilization were determined by the 2-[14C]deoxyglucose method. Lidocaine-treated animals, in the absence of convulsions, exhibited decreased glucose utilization in most brain structures compared to saline-treated animals and showed no increase in aggressive behavior. In animals displaying lidocaine-kindled convulsions there were marked increases in glucose utilization in either the hippocampus and amygdala or in perirhinal cortical areas during the seizure administration; these animals also displayed long-lasting increases in irritable behavior. Seizure duration was positively correlated with the rate of glucose utilization in the hippocampus, amygdala and septum, but inversely correlated in several non-limbic areas. These data suggest that lidocaine-kindled seizures are highly localized to limbic and perirhinal structures and are associated with important behavioral consequences.

Aggression↗

Evidence for an inhibitory prejunctional P1-purinoceptor in the rat portal vein with characteristics of the A2 rather than of the A1 subtype.

The effects of adenosine (ADO) and of the adenosine analogues 5'-N-ethylcarboxamideadenosine (NECA), 2-chloroadenosine (2-CADO), L- and D-phenylisopropyladenosine (L- and D-PIA) and N6-cyclohexyladenosine (CHA) were compared on the contractile response of the isolated rat portal vein to perivascular adrenergic nerve stimulation. The order of potency at 20% inhibition of control values was NECA greater than or equal to 2-CADO = L-PIA greater than D-PIA = CHA greater than ADO. At this level of inhibition only D-PIA had a significant inhibitory effect against a matched concentration of exogenous NA. The difference in potency between L-PIA and D-PIA was approximately 3-fold. 8-Phenyltheophylline, a potent P1-purinoceptor antagonist, had a direct inhibitory effect on the tissue per se and therefore could not be used to antagonise these compounds. It is concluded that NECA, 2-CADO, L-PIA, D-PIA, CHA and ADO mediate their inhibitory effect in the rat portal vein via a prejunctional P1-purinoceptor which displays characteristics of the A2 classification, in contrast to that found to date in other adrenergic and cholinergic nerve terminals where it displays characteristics of the A1 classification.

Adenosine↗

Indirect evidence that purinergic modulation of perivascular adrenergic neurotransmission in the portal vein is a physiological process.

The effects of adenine nucleotides and nucleosides on the contractile response to perivascular nerve stimulation were compared in the isolated portal vein of rabbit, rat and guinea-pig. 2-Chloroadenosine was more potent than adenosine and ATP, which were equipotent in producing inhibition of neurogenic contractions in the rabbit and rat via prejunctional P1-purinoceptors. In contrast, neurogenic contractions of the guinea-pig portal vein were not inhibited by adenosine and were potentiated by 2-chloroadenosine and, to a lesser extent, by ATP. Fluorescence histochemical localization of quinacrine, which binds to high levels of ATP, revealed a dense perivascular nerve plexus in the portal vein of rabbit and rat but not of guinea-pig. After chemical sympathectomy, quinacrine-positive nerves persisted in the rabbit (supporting other evidence for the presence of purinergic nerves) but not in the rat (supporting other evidence for ATP as a cotransmitter in adrenergic nerves). It is concluded that a prejunctional purinergic modulatory mechanism operates in adrenergic neurotransmission in the portal vein of rabbit and rat but not guinea-pig, and it is suggested that this indicates a physiological mechanism.

2-Chloroadenosine↗

Ocular changes in patients undergoing long-term desferrioxamine treatment.

In a group of young patients with thalassaemia and iron overload treated by subcutaneous infusions of desferrioxamine we have found a number of minor alterations in retinal function. The incidence of such changes is not related to drug dosage or to ferritin level but to abnormality of the extended glucose tolerance test.

Adolescent↗

Local cerebral glucose utilization in fetal and neonatal sheep.

The newborn mammalian brain of several species has been shown to have a lower average rate of energy metabolism and a narrower range of rates in its various components than is found in maturity. In a further study of cerebral energy metabolism during development, we have employed the [14C]deoxyglucose method for measuring local cerebral glucose utilization in fetal and neonatal sheep. After establishing the lumped constant to be 0.40 and finding the rate constants for the kinetic behavior of deoxyglucose in plasma and brain to be close to those in other species, we measured the rates of glucose utilization in 44 regions of the brain. The rates were low and homogeneous in midgestation, except for those of brain stem nuclei of the auditory and vestibular systems and those of the hippocampus which were relatively high. In the last 7 wk, local rates rose approximately threefold. After birth there was a further average increase of 50% above full-term levels. The study shows that cerebral energy metabolism rises in most structures during prenatal maturation, a time when sensory stimulation is at a relatively low level and behavioral responses are minimal.

Animals↗

Hypnogenic center theory of sleep: no support from metabolic mapping in monkeys.

By comparing rates of glucose utilization in brains of monkeys in non-REM sleep and two types of awake controls, we attempted to reveal cerebral hypnogenic centers that drive organisms to sleep through increases in their neural activity. Instead we found that metabolic activity is reduced in all the putative hypnogenic centers during sleep as compared to wakefulness. The results thus offer no support for the notion of an active center that either maintains or triggers sleep.

Animals↗

Comparative effects of acute and chronic administration of amphetamine on local cerebral glucose utilization in the conscious rat.

The 2-deoxyglucose method was employed in rats following either acute or chronic administration of d-amphetamine. The drug was given either by a single intravenous and/or repeated daily intraperitoneal injections or by osmotic pumps implanted subcutaneously. Each mode of administration resulted in a specific constellation of metabolic effects. Acute doses of d-amphetamine, 5 mg/kg, stimulated glucose utilization in a number of cerebral structures, particularly the components of the extrapyramidal motor system. No effects were observed in components of the mesolimbic dopaminergic system. Repeated daily doses of 5 mg/kg for 2 weeks had no effects unless the dosage was progressively increased to toxic levels of 15 mg/kg over a 3-week period. Dosage sustained by osmotic pumps (12-15 mg/kg/day for 1 week or 6-7 mg/kg/day for 2 weeks), however, resulted in a selected increase in glucose utilization in the nucleus accumbens, an important component of the mesolimbic system. This finding may be of significance to the mechanism of amphetamine psychosis, which is sometimes regarded as a model of schizophrenia and is considered to be evidence in support of the dopamine hypothesis of the disease.

Animals↗

Cigar and pipe smoking related to four year survival of coronary patients.

Six hundred and thirty-four male patients under 60 years who survived a first attack of unstable angina or myocardial infarction were followed for a period of four years. Details of initial and follow-up smoking habits were examined. Patients who continued to smoke cigarettes or cigars had an excess mortality compared with non-smokers, with those who stopped smoking, and with cigarette smokers who changed to pipe smoking. Pipe smokers who continued smoking the pipe had an observed mortality which was greater than that of the non-smokers, but the numbers were small and the results were not statistically significant. The effect of smoking habit on mortality was not influenced by two other determinants of prognosis: age and severity of initial attack. These results confirm that the long-term prognosis of patients after unstable angina or myocardial infarction may be significantly influenced by smoking habits. They are consistent with the hypothesis that cigar and pipe smoking may have an adverse effect after myocardial infarction but further studies are needed to corroborate the association between cigar and pipe smoking and prognosis of coronary heart disease.

Adult↗