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Experimental Skills > Isolated Tissue Pharmacology > Flashcards

Isolated Tissue Pharmacology Flashcards

0
Q

What are the 2 types of organ bath experiments ?

A

Electric field stimulation

Bath stimulation

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1
Q

What types of experiment can be used to explore pharmacological properties of drugs and their receptors ?

A

Organ bath experiments

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2
Q

What is the vas deferens ?

A

Thick walled muscular tube which conducts spermatozoa from testes to urethra

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3
Q

What is the ileum ?

A

Part of the small intestine made up of layers of circular and longitudinal smooth muscle which absorbs nutrients, bile salts and vitamin b12

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4
Q

How is the smooth muscle arranged in vas deferens tissue ?

A

Inner and outer layers of longitudinal smooth muscle with a circular layer in between

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5
Q

How is the vas deferens innervated by sympathetic nervous system ?

A

By the hypogastric nerve

When it’s activated it produces peristaltic contractions

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6
Q

What are the most important neurotransmitter released by hypogastric nerve in the vas deferens ?

A

Noradrenaline and ATP are co released
NA activates alpha-1 adrenoreceptors
ATP activates P2X purinoreceptors

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7
Q

What does an isometric transducer do ?

A

Converts changes in tension to an electrical impulse that can be recorded on a computer screen

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8
Q

What type of adrenoreceptors are present pre and post synaptically ?

A

Pre- alpha-2 adrenoreceptors

Post- alpha-1 adrenoreceptors

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9
Q

What is used in field stimulation in the organ bath ?

A

Stimulator generator

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10
Q

What types of transmission does vas deferens and ileal tissue used ?

A

Vas deferens - adrenergic transmission

Ileum - cholinergic transmission

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11
Q

What is the pathway for innervation of the ileum from the CNS ?

A

Long pre ganglionic branch which releases ACh
ACh binds to nicotinic receptors in ganglia close to or within target tissue
Short post ganglionic fibre which release ACh
Binds to muscarinic receptors in the ileum

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12
Q

What are the types of muscarinic receptors and what signalling pathways do they use ?

A

5 different types
M1, M3 and M5 - linked to Gq
M2 and M4 - linked to Gi

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13
Q

What pathway are Gs and Gi proteins linked to ?

A

Adenylate Cyclase

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14
Q

What pathway is Gq protein linked to ?

A

Activates PLC
Increases IP3 - releases calcium from intracellular stores
Increases DAG - activates protein kinase c

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15
Q

What is an agonists and an antagonist at muscarinic acetylcholine receptors ?

A

Agonist - carbachol - similar structure to acetylcholine

Antagonist- atropine

16
Q

What is the pathway in vas deferens tissue from the CNS ?

A

Short pre ganglionic fibre releases acetylcholine
ACh binds to nicotinic receptor in ganglia close to CNS
Long preganglionic fibre releases NA onto alpha/beta adrenoreceptors

17
Q

Which G protein is each of the 3 families of adrenoreceptors linked to ?

A

Alpha-1 - Gq
Alpha-2 - Gi
Beta - Gs

18
Q

What are agonists and antagonists of alpha-1 receptors ?

A

Agonist - phenylephrine

Antagonist - prazosin and phentolamine

19
Q

What is an agonist and antagonist for alpha-2 receptors ?

A

Agonist- clonidine

Antagonist- yohimbine

20
Q

What is an agonist and antagonist of beta receptors ?

A

Agonist- salbutamol and isoprene line

Antagonist - propranolol

21
Q

What receptors are present in cardiac/ventricular tissue and what are the agonist and antagonists at this tissue ?

A

Beta-1 for contractions
Agonist- NA adrenaline and isoprene line
Antagonist- propranolol

22
Q

What are the receptors present at tracheal smooth muscle and what are the agonist and antagonists at this tissue ?

A

Beta-2 for relaxation
Agonists- NA adrenaline and isoprene line
Antagonists - propranolol

23
Q

What are the receptors present at vas deferens tissue and what are the agonists and antagonists at this tissue ?

A

Postsynaptic ally alpha-1 for contraction
Presynaptic ally alpha-2
Agonists - NA adrenaline, alpha-1 phenylephrine and alpha-2 clonidine
Antagonists- Alpha-1 prazosin, phentolamine and alpha-2 yohimbine

24
Q

What receptors are present at aortic smooth muscle and what are the agonist and antagonists present at this tissue ?

A

Alpha-1 for contraction
Beta-2 for relaxation
Agonists- NA adrenaline, alpha-1 phenylephrine and beta-2 isoprenaline
Antagonists- alpha-1 prazosin and beta-2 propranolol

25
Q

What receptors are present in ileal smooth muscle and what are the agonist and antagonists present in this tissue ?

A

Muscarinic receptors
Agonists - carbachol
Antagonist- atropine

26
Q

What happened when the vas deferens was stimulated by field stimulation at 10Hz and 30Hz ?

A

The response at 30Hz was greater because it was a greater frequency so produced a greater number of action potentials so there was a larger contraction

27
Q

What was the contraction like in the vas deferens tissue ?

A

Initially rapid response causing phasic contraction by ATP (linked to ligand gates ion channel) then a slower respond causing tonic contraction via noradrenaline

28
Q

How are contractions generated in field stimulation ?

A

They are caused by releasing neurotransmitter from tissue within the prep (variscocities)

29
Q

What effects does clonidine have at contraction of vas deferens tissue and what happens to this effects when yohimbine is added ?

A

Clonidine reduces contraction
- it’s an alpha-2 agonist so it activates the alpha-2 receptors on the noradrenergic varicosity
- this is linked to Gi which decreases cAMP, reducing calcium influx so reducing NA and ATP release
Yohimbine is an alpha-2 antagonist so it competes with clonidine for the alpha-2 receptor
- reducing the effects of clonidine so therefore increases the release of noradrenaline. So increasing contraction
This only applies in field stimulation because in bath stimulation you are only activating postsynaptic receptors

30
Q

What is a major difference between field stimulation and bath stimulation ?

A

In field stimulation you are activating both pre and post synaptic receptors whereas in bath stimulation you are on it activating postsynaptic receptors because there are no action potentials being sent down the pre synaptic cell

31
Q

In bath stimulation carbachol is added to he ileal tissue and this induces contraction. What happens to this response when atropine and phentolamine are added ?

A

Atropine reduces the response because it is a muscarinic antagonist so it blocks the effects of carbachol reducing contraction.
Phentolamine is an alpha-1 antagonist so it has no effect becaus it cannot bind to the muscarinic receptors

32
Q

In bath stimulation with phenylephrine on vas deferens tissue, contraction occurs. What happens when atropine is added and phentolamine is added ?

A

Atropine has no effect becaus it is a muscarinic antagonist

Phentolamine is alpha antagonist so it reduces the response by competing with phenylephrine for the alpha-1 receptors

33
Q

What do concentration response curves allow the calculation of ?

A

The potency of the agonist

An agonist closure to the left has a greater potency because it requires less concentration to produce a response

34
Q

What is schild analysis used for ?

A

Looking at the affinity of antagonists

35
Q

Aortic smooth muscle was stimulated by the addition of phenylephrine and then prazosin was added and his reduced the response. Isoprenaline was added instead of prazosin and this also reduce the response, why ? Then propranolol was added alongside the phenylephrine and this prevented the effects of isoprenaline, why ?

A

The addition of prazosin reduced the response caused by phenylephrine because it is an alpha-1 antagonist so it competed for the alpha-1 receptors with phenylephrine.
When isoprenaline was added the repos e of the tissue was also reduced becaus isoprenaline is beta agonist so it induced relaxation of the tissue which therefore reduced the activity of the tissue.
When propranolol was added alongside phenylephrine the response once isoprenaline was added didn’t reduce because propranolol is a beta blocker so therefore it prevented isoprenaline inducing relaxation

Experimental Skills (8 decks)

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