The Same Opioid Peptide Behaves Differently at Pre-Synaptic vs Post-Synaptic Receptors
Post-synaptic mu/delta receptors controlling dopamine signaling showed different opioid peptide preferences than pre-synaptic mu, delta, and kappa receptors in the striatum.
Quick Facts
What This Study Found
Post-synaptic mu/delta receptors inhibiting DA-stimulated adenylate cyclase showed different endogenous peptide affinity profiles than presynaptic mu, delta, and kappa receptors.
Key Numbers
How They Did This
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.
Why This Research 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.
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.
What This Study Doesn't Tell Us
In vitro brain slice study. Complex pharmacology with multiple simultaneous drug exposures. Conditions may not perfectly reflect in vivo signaling.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Location-dependent affinity The same endogenous opioid peptides showed different binding profiles at pre-synaptic vs post-synaptic receptors in the striatum
- Evidence Grade:
- Preliminary — in vitro brain slice study with complex pharmacological conditions. Provides important mechanistic insight but in an artificial setting.
- Study Age:
- Published in 1993 (33 years ago). The concept of location-dependent receptor pharmacology is now well-established.
- Original Title:
- 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.
- Published In:
- The Journal of pharmacology and experimental therapeutics, 267(1), 205-10 (1993)
- Authors:
- Schoffelmeer, A N, De Vries, T J, Hogenboom, F, Mulder, A H
- Database ID:
- RPEP-00277
Evidence Hierarchy
Frequently Asked Questions
What's the difference between pre-synaptic and post-synaptic receptors?
Pre-synaptic receptors sit on nerve terminals and control neurotransmitter release. Post-synaptic receptors sit on the receiving neuron and affect its response. Even when both are opioid receptors, they can prefer different peptides and produce different effects.
Why does this make opioid drugs complicated?
A single opioid drug activates receptors in both locations simultaneously, but they respond differently. This creates complex, sometimes contradictory effects that are hard to predict or control with a single drug.
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Cite This Study
https://rethinkpeptides.com/research/RPEP-00277APA
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.
MLA
Schoffelmeer, A N, et al. "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, 1993.
RethinkPeptides
RethinkPeptides Research Database. "Mu- and delta-opioid receptors inhibitorily linked to dopami..." RPEP-00277. Retrieved from https://rethinkpeptides.com/research/schoffelmeer-1993-mu-and-deltaopioid-receptors
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.