Adenylyl cyclase catalytic activity, model specified

evidence_span

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experimental_model

Biochemistry of the cannabinoid adenylate cyclase response in neuroblastoma membranes

exposure

Guanine nucleotide dependence of the response

limitations

The biochemical companion paper establishing G-protein dependence.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Cultured neuroblastoma cells

plain_language

The inhibition runs through a G protein, as a receptor response should.

primary_references

[thc-p2984538] Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. (1985). https://pubmed.ncbi.nlm.nih.gov/2984538/ DOI: 10.1016/s0026-895x(25)12377-8

tissue_or_cell_type

Cell membranes

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 166–177

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry of the cannabinoid adenylate cyclase response in neuroblastoma membranes · source_derived_draft · unverified_draft

### thc-ac-inhibition-biochemistry The biochemistry of the cannabinoid inhibition of adenylate cyclase in neuroblastoma membranes showed the response to be guanine-nucleotide dependent. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The inhibition runs through a G protein, as a receptor response should. organism: Cultured neuroblastoma cells tissue_or_cell_type: Cell membranes experimental_model: Biochemistry of the cannabinoid adenylate cyclase response in neuroblastoma membranes limitations: The biochemical companion paper establishing G-protein dependence. exposure: Guanine nucleotide dependence of the response evidence_span: {"source_cache": "artifacts/thc-research/2984538.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1ac047a734fcf178fc62cc2e117533f5ebc2b0779132c0315d3d954c4c728e5", "start_char": 0, "end_char": 1743, "text_sha256": "e1ac047a734fcf178fc62cc2e117533f5ebc2b0779132c0315d3d954c4c728e5"} [thc-p2984538] Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. (1985). https://pubmed.ncbi.nlm.nih.gov/2984538/ DOI: 10.1016/s0026-895x(25)12377-8

evidence_span

{"source_cache": "artifacts/thc-research/8515284.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d", "start_char": 0, "end_char": 1015, "text_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d"}

experimental_model

Receptor binding and adenylate cyclase assays with anandamide

exposure

Anandamide against cannabinoid receptors and cyclase

limitations

Confirms the endogenous ligand reproduces the receptor signature of the drug.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rat brain preparations

plain_language

The natural ligand does the same thing to the same enzyme as the drug.

primary_references

[thc-p8515284] Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. (1993). https://pubmed.ncbi.nlm.nih.gov/8515284/ DOI: 10.1111/j.1471-4159.1993.tb03576.x

tissue_or_cell_type

Brain membranes

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 257–268

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding and adenylate cyclase assays with anandamide · source_derived_draft · unverified_draft

### thc-anandamide-inhibits-cyclase Anandamide interacted specifically with cannabinoid receptors and inhibited adenylate cyclase, reproducing the signature response of the plant cannabinoids. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The natural ligand does the same thing to the same enzyme as the drug. organism: Rat brain preparations tissue_or_cell_type: Brain membranes experimental_model: Receptor binding and adenylate cyclase assays with anandamide limitations: Confirms the endogenous ligand reproduces the receptor signature of the drug. exposure: Anandamide against cannabinoid receptors and cyclase evidence_span: {"source_cache": "artifacts/thc-research/8515284.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d", "start_char": 0, "end_char": 1015, "text_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d"} [thc-p8515284] Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. (1993). https://pubmed.ncbi.nlm.nih.gov/8515284/ DOI: 10.1111/j.1471-4159.1993.tb03576.x

evidence_span

{"source_cache": "artifacts/thc-research/6092901.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5", "start_char": 0, "end_char": 1329, "text_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5"}

experimental_model

Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes

exposure

Cannabinoid concentration-response on adenylate cyclase

limitations

One of the two founding pharmacology papers for Gi coupling. A transformed cell line, and cAMP is a proximal readout.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Cultured neuroblastoma cells

plain_language

The drug turns down the enzyme that makes the cell’s main second messenger.

primary_references

[thc-p6092901] Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. (1984). https://pubmed.ncbi.nlm.nih.gov/6092901/ DOI: 10.1016/s0026-895x(25)15066-9

tissue_or_cell_type

Cell membranes

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 153–164

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes · source_derived_draft · unverified_draft

### thc-cannabinoid-inhibits-ac Cannabinoids inhibited adenylate cyclase in neuroblastoma cell membranes with a pharmacology matching their psychoactivity. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The drug turns down the enzyme that makes the cell’s main second messenger. organism: Cultured neuroblastoma cells tissue_or_cell_type: Cell membranes experimental_model: Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes limitations: One of the two founding pharmacology papers for Gi coupling. A transformed cell line, and cAMP is a proximal readout. exposure: Cannabinoid concentration-response on adenylate cyclase evidence_span: {"source_cache": "artifacts/thc-research/6092901.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5", "start_char": 0, "end_char": 1329, "text_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5"} [thc-p6092901] Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. (1984). https://pubmed.ncbi.nlm.nih.gov/6092901/ DOI: 10.1016/s0026-895x(25)15066-9

evidence_span

{"source_cache": "artifacts/thc-research/2165569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db", "start_char": 0, "end_char": 1256, "text_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db"}

experimental_model

Cloning and heterologous expression of a complementary DNA from rat brain

exposure

Cannabinoid binding and adenylate cyclase inhibition in the transfected cells

limitations

The founding cloning paper. It establishes a receptor, which is what displaced the membrane-disruption explanation of cannabinoid action.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Rat receptor expressed in cells

plain_language

Cannabis acts on a specific receptor, not by melting cell membranes as was assumed.

primary_references

[thc-p2165569] Structure of a cannabinoid receptor and functional expression of the cloned cDNA. (1990). https://pubmed.ncbi.nlm.nih.gov/2165569/ DOI: 10.1038/346561a0

tissue_or_cell_type

Brain and neural cell lines

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 62–73

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and heterologous expression of a complementary DNA from rat brain · source_derived_draft · unverified_draft

### thc-cb1-cloned A cloned complementary DNA encoded a G protein-coupled receptor that inhibits adenylate cyclase in a dose-dependent, stereoselective and pertussis-toxin-sensitive manner, is more responsive to psychoactive than to non-psychoactive cannabinoids, and whose messenger RNA is found in the brain regions that have cannabinoid receptors. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Cannabis acts on a specific receptor, not by melting cell membranes as was assumed. organism: Rat receptor expressed in cells tissue_or_cell_type: Brain and neural cell lines experimental_model: Cloning and heterologous expression of a complementary DNA from rat brain limitations: The founding cloning paper. It establishes a receptor, which is what displaced the membrane-disruption explanation of cannabinoid action. exposure: Cannabinoid binding and adenylate cyclase inhibition in the transfected cells evidence_span: {"source_cache": "artifacts/thc-research/2165569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db", "start_char": 0, "end_char": 1256, "text_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db"} [thc-p2165569] Structure of a cannabinoid receptor and functional expression of the cloned cDNA. (1990). https://pubmed.ncbi.nlm.nih.gov/2165569/ DOI: 10.1038/346561a0

evidence_span

{"source_cache": "artifacts/thc-research/9070350.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c", "start_char": 0, "end_char": 2231, "text_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c"}

experimental_model

Expression and adenylate cyclase modulation across immune cell populations

exposure

Cannabinoid agonists with cAMP measurement

limitations

Maps which immune cells carry which receptor. Expression and cAMP modulation are measured; immune function outcomes are not.

nutrient_topic

THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC

organism

Mouse and human immune cells

plain_language

Immune cells carry the second receptor and respond through the same messenger.

primary_references

[thc-p9070350] Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. (1997). https://pubmed.ncbi.nlm.nih.gov/9070350/ DOI: 10.1006/taap.1996.8034

tissue_or_cell_type

Immune system

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 101–112

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression and adenylate cyclase modulation across immune cell populations · source_derived_draft · unverified_draft

### thc-cb2-immune CB1 and CB2 receptors were characterised for expression and adenylate cyclase modulation within the immune system. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Immune cells carry the second receptor and respond through the same messenger. organism: Mouse and human immune cells tissue_or_cell_type: Immune system experimental_model: Expression and adenylate cyclase modulation across immune cell populations limitations: Maps which immune cells carry which receptor. Expression and cAMP modulation are measured; immune function outcomes are not. exposure: Cannabinoid agonists with cAMP measurement evidence_span: {"source_cache": "artifacts/thc-research/9070350.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c", "start_char": 0, "end_char": 2231, "text_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c"} [thc-p9070350] Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. (1997). https://pubmed.ncbi.nlm.nih.gov/9070350/ DOI: 10.1006/taap.1996.8034

evidence_span

{"source_cache": "artifacts/melatonin-research/7946354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f", "start_char": 0, "end_char": 1054, "text_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f"}

experimental_model

Receptor cloning, radioligand binding and functional expression

exposure

Heterologous COS-7 binding and NIH3T3 functional assays

limitations

Species differ across experiments. High-affinity radioligand binding is separated from the sheep functional assay.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human and sheep MT1 in cells; functional cyclase assay used sheep receptor

plain_language

The receptor connects to an inhibitory signaling system.

primary_references

[melatonin-p7946354] Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. (1994). https://pubmed.ncbi.nlm.nih.gov/7946354/ DOI: 10.1016/0896-6273(94)90055-8

tissue_or_cell_type

Melatonin receptor identification

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 370–381

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor cloning, radioligand binding and functional expression · source_derived_draft · unverified_draft

### melatonin-mt1-sheep-cyclase The sheep MT1 receptor inhibited adenylyl cyclase through a pertussis-toxin-sensitive mechanism in transfected cells. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The receptor connects to an inhibitory signaling system. organism: Human and sheep MT1 in cells; functional cyclase assay used sheep receptor tissue_or_cell_type: Melatonin receptor identification experimental_model: Receptor cloning, radioligand binding and functional expression limitations: Species differ across experiments. High-affinity radioligand binding is separated from the sheep functional assay. exposure: Heterologous COS-7 binding and NIH3T3 functional assays evidence_span: {"source_cache": "artifacts/melatonin-research/7946354.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f", "start_char": 0, "end_char": 1054, "text_sha256": "4eed36768519d1c02ed67434eb3dc08eb561de445d3532113e7eaeb2827e021f"} [melatonin-p7946354] Cloning and characterization of a mammalian melatonin receptor that mediates reproductive and circadian responses. (1994). https://pubmed.ncbi.nlm.nih.gov/7946354/ DOI: 10.1016/0896-6273(94)90055-8

evidence_span

{"source_cache": "artifacts/melatonin-research/7568007.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f", "start_char": 0, "end_char": 1269, "text_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f"}

experimental_model

Human receptor cloning and functional expression

exposure

Radioligand binding and adenylyl cyclase measurements

limitations

Receptor overexpression system; no claim a given oral dose produces the same occupancy in every human tissue.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human MT2 expressed in COS-1 and NIH3T3 cells

plain_language

The second receptor can also reduce the signal that generates cAMP.

primary_references

[melatonin-p7568007] Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. (1995). https://pubmed.ncbi.nlm.nih.gov/7568007/ DOI: 10.1073/pnas.92.19.8734

tissue_or_cell_type

Second melatonin receptor subtype

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 383–394

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human receptor cloning and functional expression · source_derived_draft · unverified_draft

### melatonin-mt2-cyclase Human MT2 expression supported melatonin-receptor-mediated inhibition of adenylyl cyclase. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The second receptor can also reduce the signal that generates cAMP. organism: Human MT2 expressed in COS-1 and NIH3T3 cells tissue_or_cell_type: Second melatonin receptor subtype experimental_model: Human receptor cloning and functional expression limitations: Receptor overexpression system; no claim a given oral dose produces the same occupancy in every human tissue. exposure: Radioligand binding and adenylyl cyclase measurements evidence_span: {"source_cache": "artifacts/melatonin-research/7568007.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f", "start_char": 0, "end_char": 1269, "text_sha256": "1873168e5fa570a1dec0bc112045a3bcffda494e92b52f3349c8b1afebbb505f"} [melatonin-p7568007] Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor. (1995). https://pubmed.ncbi.nlm.nih.gov/7568007/ DOI: 10.1073/pnas.92.19.8734

evidence_span

{"source_cache": "artifacts/cold-research/7738011.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1c5506f21f40d6674727a5fc3344f2b02f7fc9f2f1e911fd04bfecfc2399175", "start_char": 0, "end_char": 2592, "text_sha256": "b1c5506f21f40d6674727a5fc3344f2b02f7fc9f2f1e911fd04bfecfc2399175"}

experimental_model

Immortalized mouse brown adipocyte cell lines with selective beta-adrenergic agonists and antagonists

exposure

Norepinephrine, the beta-3 selective agonist CL316,243, and subtype-selective antagonists

limitations

A cell-line dissection of receptor subtypes. The additive cAMP response indicates the subtypes are not redundant, but these are immortalized cells.

nutrient_topic

Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. · Cold water immersion

organism

Mouse cell lines

plain_language

Three different receptors for the same messenger all feed the heat gene, and together they do more than any one alone.

primary_references

[cold-p7738011] Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines. (1995). https://pubmed.ncbi.nlm.nih.gov/7738011/ DOI: 10.1074/jbc.270.18.10723

tissue_or_cell_type

Brown adipocytes

Cold water immersion: cold sensing, heat production, the catecholamine axis and what repeated exposure changes (2026-09-19) · lines 364–375

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immortalized mouse brown adipocyte cell lines with selective beta-adrenergic agonists and antagonists · source_derived_draft · unverified_draft

### cold-beta-receptors-ucp1 UCP1 expression could be induced by any of the beta-1, beta-2 or beta-3 adrenergic receptor subtypes, but the greatest response came from stimulating all three simultaneously, and beta-3 stimulation did not prevent norepinephrine from further raising adenylyl cyclase activity, suggesting an additive cAMP response. Condition category: normal nutrient_topic: Cold water immersion research collection; topical membership is not evidence of a direct clinical effect, and a therapeutic exposure is not a dietary intake. plain_language: Three different receptors for the same messenger all feed the heat gene, and together they do more than any one alone. organism: Mouse cell lines tissue_or_cell_type: Brown adipocytes experimental_model: Immortalized mouse brown adipocyte cell lines with selective beta-adrenergic agonists and antagonists limitations: A cell-line dissection of receptor subtypes. The additive cAMP response indicates the subtypes are not redundant, but these are immortalized cells. exposure: Norepinephrine, the beta-3 selective agonist CL316,243, and subtype-selective antagonists evidence_span: {"source_cache": "artifacts/cold-research/7738011.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b1c5506f21f40d6674727a5fc3344f2b02f7fc9f2f1e911fd04bfecfc2399175", "start_char": 0, "end_char": 2592, "text_sha256": "b1c5506f21f40d6674727a5fc3344f2b02f7fc9f2f1e911fd04bfecfc2399175"} [cold-p7738011] Regulation of the uncoupling protein gene (Ucp) by beta 1, beta 2, and beta 3-adrenergic receptor subtypes in immortalized brown adipose cell lines. (1995). https://pubmed.ncbi.nlm.nih.gov/7738011/ DOI: 10.1074/jbc.270.18.10723