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| Question | Answer |
| Neurotransmitters: Established (we know they are neurotransmitters and what they do) | - Acetylcholine - Noradrenaline - Dopamine - GABA - ATP |
| Neurotransmitters: Putative- unsure if neurotransmitters or not | - Histamine - Adenosine - Taurine - Carbon monoxide - Hydrogen sulphide |
| Steps in establishing a neurotransmitter | - Identify biological activity of tissue extract - Identify active principle - Satisfy the 7 criteria for a neurotransmitter - Identification of physiological roles |
| 7 criteria for a neurotransmitter | 1. mimics nerve response 2. has synthesis pathway in the nerve 3. has a storage mechanism in the nerve 4. has a release mechanism form the nerve; often calcium dependent 5. specific receptor activation 6. action ceases quickly and by enzymatic degregation or neuronal/extraneuronal uptake. |
| Noradrenaline- establishment as a neurotransmitter: Identification of biological activity | Oliver and Schafer: studied aqueous extracts of adrenal glands. - Extract increased HR of frog - Increased BP of dog - active extract was found only in the adrenal medulla and not in the adrenal cortex |
| Noradrenaline: identification of active principle | Langley- effects of adrenal extract similar to those of sympathetic nerve activation Elliot- adrenaline mimics effects of sympathetic nerves; is a closer mimic than adrenaline. Measured on responses to pilo erection and bladder compared to nerve responses. |
| Noradrenaline: presence in the nerve | Identification using histology: noradrenaline+formaldehyde= flourescent product |
| Noradrenaline; synthesis in nerve | - tyrosine enters the cell and is turned into dopa by tyrosine hydroxylase. - dopa is then converted into dopamine by dopa decarboxylase - Dopamine then converted into noradrenaline by dopamine-b-hydroxylase. |
| Noradrenaline: storage in the nerve | - 'small granular vesicles' that can be detected by electron microscopy; these concentrate and protect the neurotransmitter from degregation by mono-amine oxidase. - Vesicles can be separated from nerves by ultracentrifugation so transmitter contents can be analysed. |
| Noradrenaline: release from the nerve | Finkleman using rabbit jejunum; more modern= radiolabelled transmitter and chromotography |
| Noradrenaline: activation of specific receptors | - Proposed different receptors it activated, based on potency ratios. - Concept validated by: Differing antagonist affinities Differing radioligand binding affinities Differing transduction Molecular biology |
| Noradrenaline: mechanism for swift termination of action | - studies showed it was inactivated by uptake via transporter proteins |
| Summary: Noradrenaline as an established neurotransmitter | - Mimics nerve action- more similarly than adrenaline - Presence in nerve can be identified by flourescence - Is synthesised in the nerve from tyrosine - Stored in the nerve in vesicles - release is ca+ dependent - Has specific receptors: alpha 1 and alpha 2 adrenoreceptors - Action ceases fast through cessation of uptake |
| Importance of identifying transmitters | - Facilitates understanding of disease mechanisms and allows development of selective drugs as therapeutic agents. |
| Drugs developed from knowledge about noradrenaline | - Hypertension: beta blockers, propanolol alpha blockers, prazosin storage inhibitors, reserpine synthesis inhibitors, AMPT - Heart failiure: beta blockers, metoprolol - Depression: reuptake inhibitors, imipramine |
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