Component

Heterotrimeric Gi/o proteins

Heterotrimeric Gi/o proteins. Species, exposure and limitations are retained in each linked claim.

4 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. The biochemistry of the cannabinoid inhibition of adenylate cyclase in neuroblastoma membranes showed the response to be guanine-nucleotide dependent.

    Heterotrimeric Gi/o proteins → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
    Experimental context and source evidence
    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"}
    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
    Complete structured claim and evidence

What acts on it

  1. The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex.

    Human cannabinoid receptor 2 / CB2 / CNR2 → Heterotrimeric Gi/o proteins source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/thc-research/32004460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92", "start_char": 0, "end_char": 885, "text_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92"}
    experimental_model
    Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi
    exposure
    Agonist-bound receptor coupled to Gi
    limitations
    Captures the active, G-protein-coupled state rather than an antagonist-bound one, which is what makes the coupling claim structural rather than inferred.
    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
    Human receptor complex
    plain_language
    The receptor was caught in the act of holding its signalling partner.
    primary_references
    [thc-p32004460] Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. (2020). https://pubmed.ncbi.nlm.nih.gov/32004460/ DOI: 10.1016/j.cell.2020.01.007
    tissue_or_cell_type
    Purified signalling complex

    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 140–151

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi · source_derived_draft · unverified_draft

    ### thc-cb2-gi-structure The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex. 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 receptor was caught in the act of holding its signalling partner. organism: Human receptor complex tissue_or_cell_type: Purified signalling complex experimental_model: Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi limitations: Captures the active, G-protein-coupled state rather than an antagonist-bound one, which is what makes the coupling claim structural rather than inferred. exposure: Agonist-bound receptor coupled to Gi evidence_span: {"source_cache": "artifacts/thc-research/32004460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92", "start_char": 0, "end_char": 885, "text_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92"} [thc-p32004460] Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. (2020). https://pubmed.ncbi.nlm.nih.gov/32004460/ DOI: 10.1016/j.cell.2020.01.007
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. 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.

    Human cannabinoid receptor 1 / CB1 / CNR1 → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
    Experimental context and source evidence
    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
    Complete structured claim and evidence

  2. In n-3-deficient mice, presynaptic CB1 receptors that normally respond to endocannabinoids were uncoupled from their effector Gi/o proteins.

    Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids → Coupling of presynaptic CB1 receptors to their Gi/o effector proteins source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"}
    experimental_model
    Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays
    exposure
    Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids
    limitations
    A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change.
    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
    plain_language
    The receptor was still there but no longer connected to what it talks to.
    primary_references
    [thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
    tissue_or_cell_type
    Prelimbic prefrontal cortex and accumbens
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    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 634–645

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays · source_derived_draft · unverified_draft

    ### thc-n3-uncouples-cb1 In n-3-deficient mice, presynaptic CB1 receptors that normally respond to endocannabinoids were uncoupled from their effector Gi/o proteins. Condition category: nutrient_deficiency 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 receptor was still there but no longer connected to what it talks to. organism: Mouse tissue_or_cell_type: Prelimbic prefrontal cortex and accumbens experimental_model: Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays limitations: A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change. exposure: Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids evidence_span: {"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"} [thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards