Post-synaptic mu/delta receptors controlling dopamine signaling showed different opioid peptide preferences than pre-synaptic mu, delta, and kappa receptors in the striatum.
Location-dependent affinityThe same endogenous opioid peptides showed different binding profiles at pre-synaptic vs post-synaptic receptors in the striatum
What the researchers found
Post-synaptic mu/delta receptors inhibiting DA-stimulated adenylate cyclase showed different endogenous peptide affinity profiles than presynaptic mu, delta, and kappa receptors.
Why it matters
The same opioid peptide can have different effects depending on which receptor population it reaches. This explains some of the complexity and unpredictability of opioid drug effects.
How the study worked
Rat striatal slices superfused with dopamine. Opioid peptides tested for ability to inhibit DA D1-stimulated adenylate cyclase (postsynaptic) vs. presynaptic modulation. Peptidase inhibitors included.
What this study cannot tell us
In vitro brain slice study. Complex pharmacology with multiple simultaneous drug exposures. Conditions may not perfectly reflect in vivo signaling.
How to read the evidence
Preliminary — in vitro brain slice study with complex pharmacological conditions. Provides important mechanistic insight but in an artificial setting.
When this study was published
Published in 1993 (33 years ago). The concept of location-dependent receptor pharmacology is now well-established.
The bigger picture
This adds another layer of opioid system complexity: even within the same brain region, receptors at different positions in the circuit respond differently to the same peptides. This helps explain why opioid drugs have unpredictable and varied effects.
Questions still open
- Can drugs be designed to target pre-synaptic vs post-synaptic opioid receptors selectively?
- Does this receptor location effect contribute to the complexity of opioid side effects?
Common questions
What's the difference between pre-synaptic and post-synaptic receptors?
Why does this make opioid drugs complicated?
Read the original research
Mu- and delta-opioid receptors inhibitorily linked to dopamine-sensitive adenylate cyclase in rat striatum display a selectivity profile toward endogenous opioid peptides different from that of presynaptic mu, delta and kappa receptors.
The Journal of pharmacology and experimental therapeutics, 267(1), 205-10
Citation
Schoffelmeer, A N; De Vries, T J; Hogenboom, F; Mulder, A H. (1993). Mu- and delta-opioid receptors inhibitorily linked to dopamine-sensitive adenylate cyclase in rat striatum display a selectivity profile toward endogenous opioid peptides different from that of presynaptic mu, delta and kappa receptors.. The Journal of pharmacology and experimental therapeutics, 267(1), 205-10.