Characterization and effects on cAMP accumulation of adrenomedullin and calcitonin gene‐related peptide (CGRP) receptors in dissociated rat spinal cord cell culture
Bibliographic record
Abstract
Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) have structural similarities, interact with each others receptors (calcitonin receptor-like receptor (CLR)/receptor-activity-modifying proteins (RAMPs)) and show overlapping biological activities. AM and CGRP receptors are chiefly coupled to cAMP production. In this study, a method of primary dissociated cell culture was used to investigate the presence of AM and CGRP receptors and their effects on cAMP production in embryonic spinal cord cells. Both neuronal and non-neuronal CLR immunopositive cells were present in our model. High affinity, specific [(125)I]-AM binding sites (K(d) 79 +/- 9 pM and B(max) 571 +/- 34 fmol mg(-1) protein) were more abundant than specific [(125)I]-CGRP binding sites (K(d) 12 +/- 0.7 pM and B(max) 32 +/- 2 fmol mg(-1) protein) in embryonic spinal cord cells. Specific [(125)I]-AM binding was competed by related molecules with a ligand selectivity profile of rAM > hAM(22-52) > rCGRPalpha > CGRP(8-37) >> [r-(r(*),s(*))]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl]pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide (BIBN4096BS). Specific [(125)I]-CGRP binding was competed by rCGRPalpha > rAM > or = CGRP(8-37) > or = BIBN4096BS > hAM(22-52). Cellular levels of cAMP were increased by AM (pEC(50) 10.2 +/- 0.2) and less potently by rCGRPalpha (pEC(50) 8.9 +/- 0.4). rCGRPalpha-induced cAMP accumulation was effectively inhibited by CGRP(8-37) (pA(2) 7.63 +/- 0.44) and hAM(22-52) (pA(2) 6.18 +/- 0.21) while AM-stimulation of cAMP levels was inhibited by CGRP(8-37) (pA(2) 7.41+/- 0.15) and AM(22-52) (pA(2) 7.26 +/- 0.18). BIBN4096BS only antagonized the effects of CGRP (pA(2) 8.40 +/- 0.30) on cAMP accumulation. These pharmacological profiles suggest that effects of CGRP are mediated by the CGRP(1) (CLR/RAMP1) receptor in our model while those of AM are related to the activation of the AM(1) (CLR/RAMP2) receptor subtype.
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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) | 0.001 | 0.001 |
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".