Isolated Tissue Pharmacology

Question 0

What are the 2 types of organ bath experiments ?

Answer 0

Electric field stimulation

Bath stimulation

Question 1

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

Answer 1

Organ bath experiments

Question 2

What is the vas deferens ?

Answer 2

Thick walled muscular tube which conducts spermatozoa from testes to urethra

Question 3

What is the ileum ?

Answer 3

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

Question 4

How is the smooth muscle arranged in vas deferens tissue ?

Answer 4

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

Question 5

How is the vas deferens innervated by sympathetic nervous system ?

Answer 5

By the hypogastric nerve

When it’s activated it produces peristaltic contractions

Question 6

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

Answer 6

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

Question 7

What does an isometric transducer do ?

Answer 7

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

Question 8

What type of adrenoreceptors are present pre and post synaptically ?

Answer 8

Pre- alpha-2 adrenoreceptors

Post- alpha-1 adrenoreceptors

Question 9

What is used in field stimulation in the organ bath ?

Answer 9

Stimulator generator

Question 10

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

Answer 10

Vas deferens - adrenergic transmission

Ileum - cholinergic transmission

Question 11

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

Answer 11

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

Question 12

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

Answer 12

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

Question 13

What pathway are Gs and Gi proteins linked to ?

Answer 13

Adenylate Cyclase

Question 14

What pathway is Gq protein linked to ?

Answer 14

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

Question 15

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

Answer 15

Agonist - carbachol - similar structure to acetylcholine

Antagonist- atropine

Question 16

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

Answer 16

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

Question 17

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

Answer 17

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

Question 18

What are agonists and antagonists of alpha-1 receptors ?

Answer 18

Agonist - phenylephrine

Antagonist - prazosin and phentolamine

Question 19

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

Answer 19

Agonist- clonidine

Antagonist- yohimbine

Question 20

What is an agonist and antagonist of beta receptors ?

Answer 20

Agonist- salbutamol and isoprene line

Antagonist - propranolol

Question 21

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

Answer 21

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

Question 22

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

Answer 22

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

Question 23

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

Answer 23

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

Question 24

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

Answer 24

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

Question 25

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

Answer 25

Muscarinic receptors Agonists - carbachol Antagonist- atropine

Question 26

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

Answer 26

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

Question 27

What was the contraction like in the vas deferens tissue ?

Answer 27

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

Question 28

How are contractions generated in field stimulation ?

Answer 28

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

Question 29

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

Answer 29

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

Question 30

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

Answer 30

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

Question 31

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 ?

Answer 31

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

Question 32

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

Answer 32

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

Question 33

What do concentration response curves allow the calculation of ?

Answer 33

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

Question 34

What is schild analysis used for ?

Answer 34

Looking at the affinity of antagonists

Question 35

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 ?

Answer 35

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