Expression and localization of adenylyl cyclases and G protein‐coupled receptors in guinea pig ileum caveolae and lipid rafts
Bibliographic record
Abstract
We examined the expression and localization of adenylyl cyclase (AC) isoforms and G protein‐coupled receptors in guinea pig ileum longitudinal smooth muscle (SM). Using non‐detergent cell fractionation and sucrose gradient centrifugation, we isolated caveolae/lipid rafts from ileal SM from Hartley guinea pigs. Buoyant fractions expressed both caveolin‐1 and caveolin‐2 but excluded α‐SM actin. Immunoblotting for AC isoforms demonstrated that ileal smooth muscle express AC3, AC5/6 and AC8. Each of these AC isoforms was detected exclusively in buoyant, caveolin‐rich fractions, consistent with findings from other cells and tissues. β 1 ‐adrenergic receptor (βAR) immunoreactivity was detected in both the buoyant and heavy fractions but prostanoid EP 2 receptors were detected only in heavy fractions. Overexpression of AC6 led to prominent AC5/6 immunoreactivity in buoyant fractions and enhanced forskolin‐ and isoproterenol‐induced cAMP accumulation but did not effect PGE 2 ‐stimulated responses. AC6 overexpression in ileum altered histamine‐induced contractions, reducing the maximal percent contraction relative to KCl without altering histamine potency. Thus, ileal SM expresses predominantly caveolar/lipid raft localized isoforms of AC that are highly co‐localized with and functionally coupled to βAR. Prostanoid EP 2 receptors do not regulate the activity of these raft‐localized AC isoforms. Overexpression of AC6 in ileal SM appears to selectively enhance β‐adrenergic receptors responses. Supported by NIH grant HL079166.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".