Lec 8- ANS 5+6

Question 1

Adrenoceptor agonists- A1

Answer 1

-Adrenaline used in treatment of cardiac arrest and anaphylaxis
A1- adrenoceptor agonist:
- Phenylephrine
-Smooth muscle contraction, except GI tract (baroreceptor reflex –> bradycardia)
-Used in acute hypotension or as topical nasal decongestant

Question 2

Adrenoceptor agonist- A2

Answer 2

• Clonidine

- Antihypertensive effect due to action at pre-synaptic receptors

Question 3

Adrenoceptor agonist- B1

Answer 3

• Dobutamine
• increase HR and force of contraction
• Used in acute HF

Question 4

Adrenoceptor B2

Answer 4

• Salbutamol and terbutaline
• Smooth muscle relaxation (endothelium dependent)
• Used in asthma
• B2- adrenoceptor agonists (clenbuterol)–> Increase rate and force of skeletal muscle contraction, increased muscle mass and tremor (via PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release)

Question 5

Adrenoceptor antagonist- Alpha

Answer 5

Non-selective e.g. phenoxybenzamine, phentolamine
-Decrease BP (A1) but also enhance reflex tachycardia (A2)
Selective A1-antagonists e.g. doxazosin, prazosin
-Used in hypertension and benign prostatic hypertrophy (decrease tone in smooth muscle of bladder neck and prostate)
-Tamsulosin is selective for A1a receptors in urinary tract

Question 6

Adrenoceptor antagonists-A2 selective

Answer 6

• Selective A2 antagonists = yohimbine

- Not clinically used

Question 7

Adrenoceptor antagonists- B

Answer 7

• Non selective- propranolol
• Partial agonists- oxprenolol
• Selective B1-antagonists- atenolol
• Labetolol and carvedilol are mixed A and B antagonists

Question 8

Adrenoceptors antagonists-B effects

Answer 8

• Decrease BP by decrease CO, decrease renin release, decrease sympathetic output from CNS
• Reflex vasoconstriction preserved
• Little effect at rest but pronounced during exercise or excitement

Question 9

Adrenoceptor antagonists- uses and side effects B antagonists

Answer 9

• Treat cardiac arrhythmias; angina; AMI; HF
• Side effects: bronchoconstriction in asthma B2; Heart block and cold extremities B2; mask symptoms of hypoglycemia; nightmares (lipid soluble)

Question 10

Dales principles

Answer 10

-A mature neurone releases the same transmitter at all of its synapses
This is now outdated:
-Co-transmission is the norm
-Presynaptic modulation –> different transmitter released
-Transmitter release can change during development/injury
-Different transmitters from different terminals

Question 11

Neuromodulation- how easy or hard it is to react to something

Answer 11

• Difficult to distinguish from neurotransmission
• Generally slower (seconds- days vs milliseconds)
• Act via a secondary messenger system (vs ligand-gated ion channels)

Question 12

NANC transmission in the CNS

Answer 12

Non-adrenergic Non-cholinergic transmitters

• Ganglionic transmission: substance P; 5-HT; GABA: dopamine
• Post ganglionic terminals: NO; ATP: vasoactive intestinal peptide (VIP); neuropeptide Y (NPY)

Question 13

NANC homotropic autoinhibition (pre-synaptic inhibition)

Answer 13

• activation of presynaptic autoreceptors inhibits further release of neurotransmitter in cholinergic and adrenergic neurons
• NA when release acts on A2

Question 14

NANC heterotrophic presynaptic inhibition

Answer 14

• Noradrenaline inhibits ACh release from parasympathetic terminals in the intestine
• Mutual inhibition in the heart

Question 15

Presynaptic modulation

Answer 15

• Presynaptic modulation is usually inhibitory; But at the MNJ stimulation of presynaptic autoreceptors enhances ACh release (see Lec 2+3)
• Co transmitters or other factors can affect transmitter release

Question 16

5-HT Serotonin

Answer 16

Actions on the ANS

• Inhibits the release of NA from sympathetic nerve terminals
• -> vasodilation in some blood vessels
• -> indirect excitatory effect on enteric neurons –> stimulates GI motility

Question 17

Postsynaptic modulation

Answer 17

• Mediators act to modify excitability or spontaneous firing of post-synaptic structure
• Neuropeptide Y (NPY) enhances NA-mediated vasoconstriction via increasing the ability of NA to cause intracellular Ca2+ release

Question 18

ATP

Answer 18

• Stored in synaptic vesicles in adrenergic and cholinergic nerve terminals
• Functions as a fast transmitter at autonomic ganglia; acts on P2x receptors- ligand-gated ion channels
• Co-transmitter with NA in sympathetic nerves: initial contraction of smooth muscle due to ATP (relaxation of GI tract)
• Co-transmitter in parasympathetic nervous system; contraction of the bladder

Question 19

Peptide mediators

Answer 19

• Acts on GPCR’s
• precursors packed into vesicles in the cell body; active peptide generated within vesicle as it moves to nerve terminal
• NPY enhances NA-mediated vasoconstriction
• Salivary glands (parasympathetic): VIP –> vasodilation; ACh –> secretion

Question 20

Nitric oxide

Answer 20

• Formed from L-arginine by action of nitric oxide synthesis (NOS)
• Activates adenylate cyclase (Increase cAMP)
• pulmonary vasodilation, gastric emptying, penile erection: sildenafil potentiates effect of NO by inhibiting breakdown of cGMP

Question 21

ATP and NA co-transmission

Answer 21

• ATP and NA are packed in the same vesicle
• ATP is released and works on ion channels giving a fast and fleeting response
• NA acts on GPCRs so gives a slower and longer acting response together they cause longer term Ca2+ influx so longer contraction
• NPY can be added to give to increase the effectiveness of NA so last far longer

Question 22

Parasympathetic co-transmission

Answer 22

• ACh works on GPCRs but is the quickest
• Then NO acts
• VIP is then the slowest response (particularly in saliva VIP gives you vasodilation meaning there is sufficient blood flow to the gland so saliva production is maintained)