67
5
Several isoforms of adenosine receptors are known, including A 1 , A 2A and A 2B and A 3
receptors. A 1 receptors are coupled with G io thus leading to inhibition of adenylyl cyclase
and decrease in cAMP. The G i β/γ-subunit can be coupled to the activation of GIRK
channels, inducing hyperpolarization and a block in neurotransmitter release. A 1 receptors are expressed in the brain cortex, hypothalamus, hippocampus and basal ganglia
(. Fig. 5.5).
A 2A and A 2B receptors are coupled to G s and mediate an increase in cellular cAMP
levels. A 2A receptors are expressed in the striatum, nucleus accumbens and olfactory
bulb of the brain. They co-localize with dopamine receptors in the brain region responsible for motor control. Hetero-oligomers of D 1 and A 2A receptors have been reported in
Box 5.2 Drug Tolerance and Dependence
The US “Controlled Substances Act” regulates drugs, which can be classified within five groups
including narcotics, depressants, stimulants, hallucinogens and anabolic steroids. Adverse effects
of these drugs include the development of physical and psychological dependence, tolerance,
and withdrawal symptoms after cessation of drug intake.
Physical dependence: the body has become adapted to the presence of a drug and responds
with physical symptoms when drug intake is stopped.
Tolerance: the effects of the drug are reduced after prolonged intake of a certain amount-to
achieve the same effects the dose needs to be increased.
Withdrawal: physical and psychological symptoms appearing when drug intake is abruptly
stopped or reduced, these may include increased blood pressure, tremors, confusion, seizures
and others, depending on the drug in question.
Psychological dependence: the person is craving for a drug.
Intracellular
A2A
A1
A3
A2B
Gsα
Giβγ
Giα
GIRK
Adenosine
Caffeine
Gqα
Giα
or
OH
OH
HO
O
N
N
N
N
NH 2
N
N
N
N
O
O
CH 3
H 3 C
CH 3
. Fig. 5.5 Schematic representation of intracellular signalling pathways at A1, A2A, A2B and A3
adenosine receptors; caffeine mainly blocks A2A-receptor signalling
5.3 · Adenosine Receptors: Caffeine
5
Several isoforms of adenosine receptors are known, including A 1 , A 2A and A 2B and A 3
receptors. A 1 receptors are coupled with G io thus leading to inhibition of adenylyl cyclase
and decrease in cAMP. The G i β/γ-subunit can be coupled to the activation of GIRK
channels, inducing hyperpolarization and a block in neurotransmitter release. A 1 receptors are expressed in the brain cortex, hypothalamus, hippocampus and basal ganglia
(. Fig. 5.5).
A 2A and A 2B receptors are coupled to G s and mediate an increase in cellular cAMP
levels. A 2A receptors are expressed in the striatum, nucleus accumbens and olfactory
bulb of the brain. They co-localize with dopamine receptors in the brain region responsible for motor control. Hetero-oligomers of D 1 and A 2A receptors have been reported in
Box 5.2 Drug Tolerance and Dependence
The US “Controlled Substances Act” regulates drugs, which can be classified within five groups
including narcotics, depressants, stimulants, hallucinogens and anabolic steroids. Adverse effects
of these drugs include the development of physical and psychological dependence, tolerance,
and withdrawal symptoms after cessation of drug intake.
Physical dependence: the body has become adapted to the presence of a drug and responds
with physical symptoms when drug intake is stopped.
Tolerance: the effects of the drug are reduced after prolonged intake of a certain amount-to
achieve the same effects the dose needs to be increased.
Withdrawal: physical and psychological symptoms appearing when drug intake is abruptly
stopped or reduced, these may include increased blood pressure, tremors, confusion, seizures
and others, depending on the drug in question.
Psychological dependence: the person is craving for a drug.
Intracellular
A2A
A1
A3
A2B
Gsα
Giβγ
Giα
GIRK
Adenosine
Caffeine
Gqα
Giα
or
OH
OH
HO
O
N
N
N
N
NH 2
N
N
N
N
O
O
CH 3
H 3 C
CH 3
. Fig. 5.5 Schematic representation of intracellular signalling pathways at A1, A2A, A2B and A3
adenosine receptors; caffeine mainly blocks A2A-receptor signalling
5.3 · Adenosine Receptors: Caffeine