77
5
neurotransmission, whereas the peptides, including opioid peptides, are co-secreted
and act on GPCRs to modulate neurotransmission. The peptidergic neuromodulatory
effects are slower and last longer than neurotransmission by classical small-molecule
neurotransmitters (Merighi et al. 2011).
Endogenous and plant-derived opioids (such as the opiate alkaloids morphine, codeine
and thebaine) bind to opioid receptors. β-Endorphin is a ligand for μ-receptors, enkephalins bind δ-receptors and dynorphins are specific for κ-receptors. Opiates, including morphine, specifically act on the μ-receptors (hence the name). The semisynthetic
diacetylmorphine, known as heroin, binds even more efficiently than morphine. Activation
of opiate receptors by endogenous or drug derived opioids inhibits release of excitatory
neurotransmitters from the presynapse and induces hyperpolarization of postsynaptic
neurons.
Μ-opioid receptors are abundant in neurons involved in pain perception. Conscious
pain has both, a sensual component, telling whether and where there is pain, and an emotional one, evaluating the pain. Thus, the neuronal network involved senses, processes,
and puts pain signals into a cognitive context. Opioids target pain transmission from the
periphery by activating descending nociceptive inhibition pathways. On the other hand,
they also modulate the emotional component of pain perception by inhibiting neurotransmission in certain areas of the brain cortex (Pasternak and Pan 2013).
A three-neuron scheme is considered to transmit pain from the periphery to the
cortex. This includes the first-order neuron, which receives pain information induced by
COOH
NH 2
Proenkephalin A
= Methionine enkephalin :
= Leucine enkephalin :
YGGFM
YGGFL
= Methionine enkephalin : YGGFM, extended by up to 3 amino acids
COOH
NH 2
Prodynorphin
= Dynorphin A: YGGFL RRIRPKLKWDNQ
COOH
NH 2
Proopiomelanocortin
= β-Endorphin: YGGFM TSEKSQTPL VTLFKNAIIKNA YKKGE
. Fig. 5.10 Schematic representation of opioid peptide precursor proteins proenkephalin A, prodynorphin and proopiomelanocortin; positions of endogenous opioid peptides within the precursors are
indicated, and the amino acid sequences of Met- and Leu-enkephalins, dynorphin A and β-endorphin are
given in single-letter code
5.7 · Opioid Receptors: Morphine, Heroin and Salvinorin A
5
neurotransmission, whereas the peptides, including opioid peptides, are co-secreted
and act on GPCRs to modulate neurotransmission. The peptidergic neuromodulatory
effects are slower and last longer than neurotransmission by classical small-molecule
neurotransmitters (Merighi et al. 2011).
Endogenous and plant-derived opioids (such as the opiate alkaloids morphine, codeine
and thebaine) bind to opioid receptors. β-Endorphin is a ligand for μ-receptors, enkephalins bind δ-receptors and dynorphins are specific for κ-receptors. Opiates, including morphine, specifically act on the μ-receptors (hence the name). The semisynthetic
diacetylmorphine, known as heroin, binds even more efficiently than morphine. Activation
of opiate receptors by endogenous or drug derived opioids inhibits release of excitatory
neurotransmitters from the presynapse and induces hyperpolarization of postsynaptic
neurons.
Μ-opioid receptors are abundant in neurons involved in pain perception. Conscious
pain has both, a sensual component, telling whether and where there is pain, and an emotional one, evaluating the pain. Thus, the neuronal network involved senses, processes,
and puts pain signals into a cognitive context. Opioids target pain transmission from the
periphery by activating descending nociceptive inhibition pathways. On the other hand,
they also modulate the emotional component of pain perception by inhibiting neurotransmission in certain areas of the brain cortex (Pasternak and Pan 2013).
A three-neuron scheme is considered to transmit pain from the periphery to the
cortex. This includes the first-order neuron, which receives pain information induced by
COOH
NH 2
Proenkephalin A
= Methionine enkephalin :
= Leucine enkephalin :
YGGFM
YGGFL
= Methionine enkephalin : YGGFM, extended by up to 3 amino acids
COOH
NH 2
Prodynorphin
= Dynorphin A: YGGFL RRIRPKLKWDNQ
COOH
NH 2
Proopiomelanocortin
= β-Endorphin: YGGFM TSEKSQTPL VTLFKNAIIKNA YKKGE
. Fig. 5.10 Schematic representation of opioid peptide precursor proteins proenkephalin A, prodynorphin and proopiomelanocortin; positions of endogenous opioid peptides within the precursors are
indicated, and the amino acid sequences of Met- and Leu-enkephalins, dynorphin A and β-endorphin are
given in single-letter code
5.7 · Opioid Receptors: Morphine, Heroin and Salvinorin A