Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 4 THE PHARMACOLOGY OF THE AUTONOMIC NERVOUS SYSTEM
Tyrosine
Tyrosine
DOPA
Dopamine
1 6
MAO
Dopamine
Noradrenaline
2
NA
(Adrenaline)
–
NA
7
Presynaptic
α 2 adrenoceptors
α 2
NA
3
4
5
Uptake 1
Vascular
system
MAO
COMT
Liver
Postsynaptic cell COMT Adrenoceptors Uptake 2
Fig 4.3 Schematic diagram of a noradrenergic varicosity (a release site of a sympathetic postganglionic nerve fiber).
The circled numbers refer to Table 4.6. COMT, catechol-0-methyl transferase; MAO, monoamine oxidase; NA,
noradrenaline (norepinephrine).
conclusions. The main reason for this was the fact that
Dale studiously ignored the logical explanation for his
observations as a result of his dislike for John N Langley,
who had first introduced the pharmacological concept
of receptor subtypes when he classified acetylcholine
receptors as nicotinic and muscarinic receptors. The
solution to the problem, the existence of adrenoceptor
subtypes, was therefore not proposed until much later,
when Raymond Ahlquist studied the effects of three
different catecholamines in different tissues, observing
different orders of potency for noradrenaline (norepinephrine),
adrenaline (epinephrine) and the synthetic
catecholamine isoprenaline.
In 1948, based on his observations, Ahlquist suggested
the following classification:
● α-adrenoceptors, where noradrenaline (norepinephrine)
and adrenaline (epinephrine) are much more
potent than isoprenaline
● β-adrenoceptors, where isoprenaline is much more
potent than noradrenaline (norepinephrine) and
adrenaline (epinephrine).
In due course, the discovery of selective adrenoceptor
antagonists resulted in the further subclassification of
adrenoceptors into α 1 and α 2 as well as β 1 , β 2 and β 3
with additional subtypes that can be identified based on
molecular differences.
All adrenergic receptors are typical 7TM G proteincoupled
receptors which can induce a wide range of
effects by coupling to specific second messenger
systems.
Table 4.7 summarizes the main characteristics of the
different adrenoceptor subtypes, their tissue distribution
and functional role.
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