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Biomedical subjects

T C Westfall

Publications and source records attributed to T C Westfall.

At least 109 records · Page 6Linked to original sources
PubMed1977

Catecholamine uptake, accumulation, and release in acute porphyria.

Hypertension and tachycardia are well known features of acute porphyria and have been shown to be related to increased circulating catecholamines. The mechanism by which circulating catecholamines are increased was studied using the isolated perfused rat heart and human platelets as a model of adrenergic neuronal function. It was found that neither delta-aminolevulinate (ALA) nor porphobilinogen (PBG) blocked uptake or caused release in the isolated perfused rat heart. Platelets from six patients with acute prophyria, three in remission and three latent, with matching normal controls were studied with regard to their uptake of [(3)H]norepinephrine in the presence of ALA or PBG. It was found that ALA and PBG significantly reduced uptake and accumulation of [(3)H]-norepinephrine in patients with acute porphyria; however, no similar reduction in uptake and accumulation was observed in the platelets of normal controls. Therefore, it appears that there is a latent defect in the catecholamine uptake and (or) accumulation of platelets of patients with acute prophyria which only manifests itself in the presence of ALA or PBG. If platelet uptake serves as a model of adrenergic neuron uptake, this suggests that elevated circulating catecholamine levels during acute attacks of acute porphyria are caused at least partially by blockade of re-uptake into the sympathetic neurons.

Acute Disease↗
PubMed1976

Nicotinic effect of acetylcholine on the release of newly synthesized (3H)dopamine in rat striatal slices and cat caudate nucleus.

The effect of acetylcholine (ACh), carbachol and nicotinic blocking agents on the release of newly synthesized [3H]dopamine ([3H]DA) was studied in vitro on rat striatal slices and in vivo on the cat caudate nucleus. In the latter case, the animals were anaesthetized with halothane; in some experimetns an 'encéphale isolé' preparation was used to eliminate anaesthesia. Rat striatal slices placed in a superfusion chamber were continuously superfused with L-[3,5-3H]tyrosine. A cup placed on the ventricular surface of the cat caudate nucleus similarly allowed a continuous superfusion of the structure with the 3H amino acid. In both cases the quantities of [3H]DA contained in serial superfusate fractions were estimated; the drugs were always added in superfusing medium. In vitro ACh (10(-5) M) and carbachol (10(-5) M) enhanced the release of [3H]DA (90%). Similar results were obtained in vivo in anaesthetized cats. The effect of ACh (10(-5) M) was more pronounced (125%) in presence of eserine (10(-4) M) than with ACh alone (65%). ACh was also effective in unanaesthetized cats. The ACh effect on [3H]DA release was reproducible within the same experiment both in vitro and in vivo. This allowed to test the effect of anticholinergic agents on the ACh induced release of [3H]DA. In vivo hexamethonium (10(-4) M, 10(-5) M) partially blocked the release of [3H]DA induced by ACh (10(-5) M) alone; the effect was not seen when ACh was added in the presence of eserine (10(-4) M). Both in vivo and in vitro the prior introduction of mecamylamine into the superfusing medium antagonized the stimulating effect of ACh (10(-5) M) on [3H]DA release. The effects of this nicotinic blocking agent were seen with various concentrations (10(-6); (10(-5) 10(-4) in the in vitro experiments.

Acetylcholine↗
PubMed1976

The role of presynaptic receptors in the release and synthesis of 3H-dopamine by slices of rat striatum.

Striatal slices were continuously superfused with L-3,5-(3)H-tyrosine (50 muCi/ml) and 4H-H2O [index of 3H-dopamine (3H-DA) synthesis] and 3H-DA estimated in 0.5 ml (2.5 min) superfusate fractions. Depolarization with 50 mM K+ for 7.5 min induced a marked increase in 3H-DA release and a biphasic effect on synthesis (slight increase in the first fraction followed by a significant decrease in the third and fourth fractions). The decrease in the rate of 4H-H2O formation induced by K+ was not related to modifications of the specific activity of tyrosine in tissues. The possibility that the inhibition of synthesis was due to alterations in DA concentration in the synaptic cleft was examined. Benztropine in a concentration which produced inhibition of DA uptake (10(-6) M) increased the K+ induced overflow of 3H-DA but failed to alter the inhibition of synthesis. On the other hand, when the powerful neuroleptic fluphenazine was added to the superfusion medium in a concentration which only weakly blocked 3H-DA uptake (10(-6) M) it potentiated 3H-DA release and prevented the inhibition of synthesis both in the absence or presence of benztropine. A similar effect was seen following the in vivo treatment of rats with fluphenazine (2 mg/kg; 1 1/2 h before sacrifice). The addition of exogenous DA (0.6 X 10(-6) M) or NA (10(-6) M) to the superfusion medium increased 3H-DA outflow and reduced DA synthesis while isoproterenol (10(-6) M) was without effect. The DA inhibitory effect on synthesis was still observed in the presence of benztropine (10(-6) M) while the NA effect was prevented. This concentration of benztropine blocked both DA and NA uptake. The administration of fluphenazine (10(-6) M) significantly prevented the decrease in 3H-DA synthesis induced by exogenous DA and partially prevented the effect of NA. In addition, the effect of exogenous DA on the inhibition of synthesis was still seen in the presence of 2-amino-4-hydroxy-6,7-dimethyl-5,6,-7,8-tetrahydropteridine hydrochloride (DMPH4) (to protect against end-product inhibition). The present results provide direct support for the concept that activation of presynaptic DA receptors located on DA terminals in the striatum of the rat results in an inhibition of synthesis and release of the transmitter.

Animals↗
PubMed1976

The effect of cyclic nucleotides on the release of 3H-dopamine from rat striatal slices.

Slices (1.0 mm thick and 0.4 cm in diameter) obtained from rat neostriatum were preincubated with 3H-dopamine (3H-DA; 0.8 mugM) for 30 minutes and then superfused at a rate of 1.0 ml/min in glass chambers (volume, 2 ml) for varying lenghts of time prior to electrical stimulation. Superfusate effluents were continuously collected and analyzed for 3H-DA and 3H-metabolites by liquid scintillation spectrometry after separation by alumina and Dowex 50 column chromatography. 3H-DA represented only a small proportion of the spontaneous overflow of radioactivity (9.8%) but represented the largest portion recovered in the tissue (55%). After electrical stimulation of the slices (biphasic square-wave pulses, 50 pulses/sec; 1.1-msec duration; supramaximal voltage), there was a marked increase in 3H-DA and all 3H-fractions. The percent increase of 3H-DA, 3H-O-methylated + 3H-O-methylated deaminated, 3H-dihydroxyphenylacetic acid and 3H-dihydroxylphenylethanol was 549, 232, 215 AND 246%, respectively. The addition to the superfusion medium of dibutyryl adenosine 3:5-monophosphate (DBcAMP) in the presence or absence of phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, 0.5 mM, or aminophylline, 5 mM) and cyclic adenosine monophosphoric acid in the presence but not the absence of the phosphodiesterase inhibitors potentiated the electrically induced release of 3H-DA. Neither cyclic nucleotide had any effect on the spontaneous overflow of 3H-DA or metabolites, the metabolism of 3H-DA or the uptake of 3H-DA into dopaminergic neurons. Guano sine 3:5-monophosphate was without effect on the electrically induced release of 3H-DA. The ED50 for the DBcAMP potentiation of hte electrically induced release of 3H-DA was 6 mugM. These results extend to the central nervous system the possibility that adenosine 3-5-monophosphate may play a role in the regulation or modulation of monoaminergic synaptic transmission.

Animals↗
PubMed1975

Inhibition of catecholamine release by tolbutamide and other sulfonylureas.

Tolbutamide and other sulfonylureas inhibited spontaneous and nicotine-induced release of catecholamines from the perfused cat adrenal gland and nicotine-induced release of [3-H]norepinephrine from isolated guinea pig hearts. Of the sulfonylureas tested, the order to potency of this inhibitory effect paralled the hypoglycemic action. These results raise the possibility that the inhibition of the sympathoadrenal system may contribute in part to the hypoglycemic action of sulfonylureas.

Adrenal Glands↗