How can experimental data show an exposure of neuronal tissue?
The experimental data demonstrate that exposure of neuronal tissue to clonidine and tyramine resulted in an increased release of 3H-Noradrenaline after electrical stimulation. Both pharmacological interventions demonstrated a pattern of increased 3H-Noradrenaline release with increasing frequency. Both drugs increased induced peak release at a frequency of 10 Hz. This trend occurs because greater frequencies cause greater electrical stimulation. As a result, presynaptic neurons fire more action potentials, resulting in enhanced noradrenaline release.
Clonidine, an alpha-2 adrenergic agonist, was predicted to decrease 3H- Noradrenaline release because it binds to and stimulates norepinephrine receptors on the pre-synaptic neuron. This binding causes the inhibition of the enzyme adenylyl cyclase, which reduces cAMP production and inhibits calcium ion influx into the neuron. Calcium ions are normally responsible for binding to synaptotagmin, thus triggering the release of vesicles containing3H- Noradrenaline into the synaptic cleft. Inhibition of calcium ion influx while therefore prevent this vesicle release. The ultimate effect is a decreased level of 3H-Noradrenaline release. Surprisingly, clonidine caused increased neurotransmitter release in the brain tissue samples. This result failed to support the proposed experimental hypothesis. Tyramine is known as a catecholamine releasing agent. It displaces catecholamines such as norepinephrine from pre-synaptic storage vesicles. Thus it was predicted that tyramine would increase 3H-Noradrenaline release in the brain tissue samples. The data support this proposed hypothesis. Tyramine increases neurotransmitter release; a nearly 14,000% increase was observed in brain tissue samples exposed to the drug along with electrical stimulation at 10 Hz. Tyramine samples, however, do not demonstrate a perfect positive relationship between the frequency of electrical stimulation and percent increase in
3H-Noradrenaline release. The percent release drops steeply after 5 Hz, and at 8
Hz the percent release begins increasing once again.