Evidence map›Paper›PMID 41946477›Full record

ArticleBritish journal of pharmacology2026

Inhibition of adenylyl cyclase 1 or exchange protein activated by cAMP restores ATP-sensitive potassium channel activity after chronic opioid exposure.

Amanda H Klein, S M Sabbir Alam, Kayla Johnson, Christian Kriner, Brie Beck, Bethany Nelson, Cassidy Hill, Belle Meyer, Jonas Mellang, Val J Watts

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in British journal of pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Morphine-inducedFrontiers in neuroscience · 2026
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Amanda H KleinDepartment of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA.
S M Sabbir AlamBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.
Kayla JohnsonDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, Minnesota, USA.
Christian KrinerDepartment of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA.
Brie BeckDepartment of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, USA.
Bethany NelsonDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, Minnesota, USA.
Cassidy HillDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, Minnesota, USA.
Belle MeyerDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, Minnesota, USA.
Jonas MellangDepartment of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota, Duluth, Minnesota, USA.
Val J WattsBorch Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana, USA.

Funding

KATP Channels as Downstream targets of adenylyl cyclases during opioid tolerance and withdrawalR01DA051876 · NIDA · UNIVERSITY OF MINNESOTA · PI KLEIN, AMANDA HELEN · 2021 to 2025
$2.9M
Pharmacological validation of adenylyl cyclase 1 as a drug target for chronic painR01NS119917 · NINDS · PURDUE UNIVERSITY · PI FLAHERTY, DANIEL PATRICK, WATTS, VAL J · 2021 to 2025
$2.0M
NIDA NIH HHS R01 DA051876NIH HHS R01DA051876NIH HHS R01NS119917NINDS NIH HHS R01 NS119917Purdue University
6 · The paper itself

Abstract

background and purposeProlonged exposure to Gαi/o-linked receptor agonists such as opioids can lead to a sensitization of adenylyl cyclases (ACs), resulting in heterologous sensitization or cyclic AMP (cAMP) overshoot. The molecular consequences of cAMP overshoot are not well understood, but this adaptive response is suggested to play a critical role in the development of opioid tolerance and withdrawal. EXPERIMENTAL APPROACH: Genetic reduction of AC1 and simultaneous upregulation of ATP-sensitive potassium channel (K KEY

resultsReduction of AC1 and upregulation of K CONCLUSION AND IMPLICATIONS: This study presents evidence for investigating further AC1 signalling as a target for opioid tolerance and withdrawal, by increasing EPAC activity and affecting potassium channels downstream of opioid receptors.

Indexed as

Adenylyl Cyclase InhibitorsAdenylyl CyclasesAnalgesics, OpioidCyclic AMPGuanine Nucleotide Exchange FactorsKATP ChannelsAnimalsCell Line, TumorHEK293 CellsHumansKcnj11 ChannelMaleMiceMice, Inbred C57BLMice, Knockoutadenylyl cyclase 1Adenylyl Cyclase InhibitorsAdenylyl CyclasesAnalgesics, OpioidCyclic AMPGuanine Nucleotide Exchange FactorsKATP ChannelsKcnj11 Channeladenylyl cyclaseATP‐sensitive potassium channel (KATP)cAMP Difference Detector in situ (cADDis)cAMP overshootexchange protein directly activated by cAMP (EPAC)opioid

Identifiers

PMID41946477
PMCPMC13208457

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.