Effects on renal sympathetic axons in dog of acute 6-hydroxydopamine treatment in combination with selective neuronal uptake inhibitors.
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1. In anaesthetized dogs, we have investigated the effect on renal responses to sympathetic nerve stimulation of acute treatment with the catecholaminergic neurotoxin 6-hydroxydopamine (2 mg kg-1 i.v.), administered alone or after blockade of neuronal catecholamine uptake pathways for noradrenaline (NA) or dopamine with desmethylimipramine or benztropine, respectively. 2. Under control conditions, renal nerve stimulation caused renal vasoconstriction, reduced glomerular filtration and sodium and water excretion and caused net efflux of NA and dopamine into the renal venous plasma. Two h after administration of 6-hydroxydopamine alone, there was abolition of both functional responses and catecholamine efflux during nerve stimulation. 3. In animals pretreated with desmethylimipramine (1 mg kg-1), 6-hydroxydopamine had no significant effect on functional responses to renal nerve stimulation and nerve-evoked efflux of NA was only moderately reduced. Efflux of dopamine was still markedly reduced by 6-hydroxydopamine, but more variably than occurred without desmethylimipramine treatment. 4. In animals pretreated with benztropine (0.2 mg kg-1), nerve-evoked efflux of dopamine, but not that of NA, was protected against reduction by 6-hydroxydopamine. A higher dose of benztropine (1 mg kg-1) protected efflux of both NA and dopamine against 6-hydroxydopamine. 5. We conclude that acute treatment with a low dose of 6-hydroxydopamine is an effective method of inactivating peripheral sympathetic nerves. The differential effects of desmethylimipramine and benztropine in preserving nerve-evoked efflux of NA and dopamine after 6-hydroxydopamine support the view that these catecholamines originate predominantly from different intrarenal axons. However, neither uptake blocker appears to be completely specific in its actions. (+info)
Effects of the histamine H(1) receptor antagonist and benztropine analog diphenylpyraline on dopamine uptake, locomotion and reward.
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Interactions of benztropine, atropine and ketamine with veratridine-activated sodium channels: effects on membrane depolarization, K+-efflux and neurotransmitter amino acid release.
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1. The effect of benztropine, atropine and ketamine on veratridine-induced efflux of K+, membrane depolarization and release of amino acid neurotransmitters was investigated in the preparation of rat brain synaptosomes. 2. All three drugs inhibited in a concentration-dependent manner the processes measured: the most effective compound was benztropine which exhibited an approximate Kd of 2 microM. The inhibition was not competitive in nature. 3. The veratridine titration curves in the presence of drugs were sigmoid with Hill coefficients of about 1.4. 4. At higher concentrations, benztropine, atropine and ketamine blocked uptake of amino acid neurotransmitters into synaptosomes. 5. It is postulated that benztropine, atropine and ketamine interfere with the veratridine-activated influx of sodium into synaptosomes through voltage-dependent channels by acting at the same site as local anaesthetics. Interactions at this site alter allosterically binding and action of veratridine. In addition, at higher concentrations the drugs interact with the carrier proteins for amino acid neurotransmitters and block their transport. (+info)