Flashcards
L8-Neurotransmitter identification and proof of function **
Cards in this deck (15)
- 1Neurotransmitters: Established (we know they are neurotransmitters and what they do)- Acetylcholine
- Noradrenaline
- Dopamine
- GABA
- ATP - 2Neurotransmitters: Putative- unsure if neurotransmitters or not- Histamine
- Adenosine
- Taurine
- Carbon monoxide
- Hydrogen sulphide - 3Steps in establishing a neurotransmitter- Identify biological activity of tissue extract
- Identify active principle
- Satisfy the 7 criteria for a neurotransmitter
- Identification of physiological roles - 47 criteria for a neurotransmitter1. 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. - 5Noradrenaline- establishment as a neurotransmitter: Identification of biological activityOliver 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 - 6Noradrenaline: identification of active principleLangley- 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. - 7Noradrenaline: presence in the nerveIdentification using histology:
noradrenaline+formaldehyde= flourescent product - 8Noradrenaline; 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. - 9Noradrenaline: 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. - 10Noradrenaline: release from the nerveFinkleman using rabbit jejunum;
more modern= radiolabelled transmitter and chromotography - 11Noradrenaline: 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 - 12Noradrenaline: mechanism for swift termination of action- studies showed it was inactivated by uptake via transporter proteins
- 13Summary: 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 - 14Importance of identifying transmitters- Facilitates understanding of disease mechanisms and allows development of selective drugs as therapeutic agents.
- 15Drugs 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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- Pharmacology l8 neurotransmitter id and proof of function
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- Rose P
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