Cardiovascular and renal effects of a highly potent mu opioid receptor agonist (cUENK6)
Bibliographic record
Abstract
The following studies were performed to investigate the cardiovascular and renal effects of a recently developed most potent mu opioid receptor agonist, cyclo (Nɛ, Nβ -carbonyl-D-Lys2, Dap5)-enkephalinamide (cUENK6). Conscious, normally hydrated rats (∼ 250 g) were injected i.v. with increasing doses of cUENK6 ( 0, 0.1, 1, 3, 5, 10 μg/300 ml saline). Renal parameters were measured in urine collected on hourly basis over 4 h post-injection. Arterial pressures and heart rate were measured by telemetry. The doses of 1, 3, and 5 μg dose dependently and significantly (n = 10-25 rats each, p< 0.01) stimulated diuresis, natriuresis, kaliuresis and urinary cGMP excretion during the 1st h post-injection, but only the cumulative 4 h diuretic response was significantly increased. During the 1st h, cUENK6 (3 μg) stimulated excretion of urine (1.1±0.2 vs 3.3± 0.3 ml/h), sodium (60±10 vs. 124±12 μeq/h), potassium (47±8 vs. 118±13 μeq/h) and cGMP (1948±559 vs. 4857± 807 pmol/h). These effects were inhibited by naloxone (0.8 mg/300 μl saline) injected 10 min prior to cUENK6 (3 μg), indicating receptor mediated actions. cUENK6 (3 μg) also inhibited the transient stress-induced increase in pressure that occurred over the first 30 min post injection, and the effect was also reversed by naloxone (n=3-6 each). Plasma ANP increased 2 h post cUENK6 (3 μg) injection from 123±11 to 192±21 pg/ml (n = 10-24, p<0.01) and the effect was associated with increased ANP mRNA (n = 7) detected by PCR in right atria (135%) and left ventricles (170%). Urinary ANP increased during the 1st h from 126±15 to 200±28 pg/h (n = 10, p<0.02), which may explain the stimulated renal responses observed during the 1st h post cUENK6 injection. The opioid-dependent cardiovascular and renal effects may have important physiological benefits.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".