ABSTRACT
1. The reserpine-like agent, Ro4-1284 (2-hydroxy-2ethyl-3-isobutyl-9,10-dimethoxy-1,2,3,4,6,7-hexahydro- 11b-[H] benzo (a)quinolizine) releases [3H]noradrenaline ([3H]NA) from prelabelled superior cervical ganglion (cell bodies) and nictitating membrane (nerve endings) of the cat. 2. The potency of Ro 4-1284 29.0 microM was higher in the cell bodies than in the nerve endings. 3. In both tissues, exposure to the reserpine-like agent Ro 4-1284 induced a selective increase in the spontaneous outflow of [3H]DOPEG, while the [3H]OMDA metabolites to the release induced by Ro 4-1284 was very small. 4. The desamination is the preferential way of the metabolic inactivation of the [3H]NA released by the reserpine-like agent in both parts of the noradrenergic neuron.
Subject(s)
2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-hexahydro-3-isobutyl-9,10-dimethoxy-/pharmacology , Nictitating Membrane/drug effects , Norepinephrine/metabolism , Superior Cervical Ganglion/drug effects , Animals , Cats , Female , In Vitro Techniques , Male , Nictitating Membrane/metabolism , Superior Cervical Ganglion/metabolismABSTRACT
1. The release and the metabolism of [3H]noradrenaline ([3H]NA) induced by tyramine was studied in the superior cervical ganglion (cell bodies) and in the nictitating membrane (nerve endings) of the cat. 2. Exposure of the ganglia to 58.0 and 174.0 microM tyramine resulted in the release of 13.7 and 11.8% respectively of the total tissue radioactivity. In the nictitating membrane, the fractional release of radioactivity was directly proportional to the concentration of tyramine (5.8, 58.0 and 174.0 microM). 3. In ganglia [3H]DOPEG accounted for 55.8% of the radioactivity released by 58.0 microM tyramine and only 10.5% of the radioactivity was unmetabolized NA. In presence of 174.0 microM tyramine, [3H]NA increased to 28.0% of the total radioactivity and [3H]DOPEG and [3H]OMDA decreased to 45.3 and 18.9% respectively. 4. In the nerve endings, the contribution of [3H]NA, [3H]DOMA and [3H]NMN increased with the concentration of tyramine while [3H]DOPEG decreased. 5. The deamination is the first step of the metabolic inactivation of [3H]NA induced by tyramine in the cell body of the postganglionic adrenergic neuron while in the nerve endings [3H]NA is preferentially O-methylated.
Subject(s)
Nictitating Membrane/drug effects , Norepinephrine/metabolism , Superior Cervical Ganglion/drug effects , Tyramine/pharmacology , Animals , Cats , Female , In Vitro Techniques , Male , Methoxyhydroxyphenylglycol/analogs & derivatives , Methoxyhydroxyphenylglycol/metabolism , Nictitating Membrane/metabolism , Superior Cervical Ganglion/metabolism , TritiumABSTRACT
The effects of two benzodiazepines, diazepam and clonazepam, were studied on the release of [3H]noradrenaline and of [3H]acetylcholine elicited by preganglionic stimulation of the cat isolated superior cervical ganglion and on the contractile responses evoked by either nerve stimulation or exogenous noradrenaline in the cat isolated nictitating membrane. Both 10 microM diazepam and 10 microM clonazepam reduced by approximately 50% the release of [3H]noradrenaline and of [3H]acetylcholine in the cat ganglion whereas they did not modify the contractile responses in the nictitating membrane. It is concluded that benzodiazepines are also peripheral neuroactive agents and that they exhibit a tissue-selective action within the same animal species.
Subject(s)
Acetylcholine/metabolism , Anti-Anxiety Agents/pharmacology , Ganglia, Sympathetic/metabolism , Norepinephrine/metabolism , Animals , Cats , Clonazepam/pharmacology , Diazepam/pharmacology , Electric Stimulation , Ganglia, Sympathetic/drug effects , Neurons/drug effects , Neurons/metabolism , Nictitating Membrane/drug effects , Nictitating Membrane/metabolismABSTRACT
The release and metabolism of 3H-noradrenaline (3H-NA) produced by d-amphetamine was studied in the superior cervical ganglion of the cat (cell bodies) and in the nictitating membrane (nerve endings). Exposure of the nictitating membrane to 10 microM d-amphetamine, resulted in the release of 5.1% of the total radioactivity. This was mainly collected as 3H-normetanephrine (3H-NMN) and as 3H-NA; 3H-3,4-dihydroxyphenylglycol (3H-DOPEG) did not contribute to the drug-induced outflow of radioactivity. In contrast, exposure of ganglionic cell bodies to 10 microM d-amphetamine for 10 min released only 1.74% of the total tissue radioactivity and 3H-DOPEG represented the most important fraction of the released radioactivity. When ganglia were exposed to 30 microM d-amphetamine, the radioactivity released was 5.2%; the proportion of 3H-NA and 3H-NMN increased and 3H-DOPEG was reduced. These results show that: a) d-amphetamine releases 3H-NA from prelabeled cell bodies and nerve endings; b) the potency of d-amphetamine was higher in nerve terminals than in cell bodies, and c) at low concentrations of d-amphetamine, the metabolism of the released neurotransmitter differed between both parts of the adrenergic neuron.