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Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide

James A. Nathanson, Paul Greengard

Proceedings of the National Academy of Sciences March 1, 1974 DOI: 10.1073/pnas.71.3.797 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Laboratory study Peer reviewed
Population Thoracic ganglia homogenates from an insect nervous system
Interventions Serotonin D-lysergic acid diethylamide (LSD) 2-bromo-LSD cyproheptadine
Topics LSD Serotonin
Keywords Cyclase Adenylate kinase 5-HT Receptor Cyproheptadine Neurotransmission Quipazine Serotonin antagonists Endocrinology Biochemistry Pharmacology
Citations 95
Key points A serotonin-sensitive adenylate cyclase in insect nervous tissue is competitively inhibited by LSD with an inhibitory constant of 5 nM, suggesting a direct link between serotonin receptors and this enzyme in serotonergic neurotransmission.

Abstract

An adenylate cyclase (EC 4.6.1.1) that is activated specifically by low concentrations of serotonin has been identified in homogenates of the thoracic ganglia of an insect nervous system. The activation of this enzyme by serotonin was selectively inhibited by extremely low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, agents which are known to block certain serotonin receptors in vivo . The inhibition was competitive with respect to serotonin, and the calculated inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase was 5 nM. The data are consistent with a model in which the serotonin receptor of neural tissue is intimately associated with a serotonin-sensitive adenylate cyclase which mediates serotonergic neurotransmission. The results are also compatible with the possibility that some of the physiological effects of LSD may be mediated through interaction with serotonin-sensitive adenylate cyclase.

Comparable studies

Other experimental studies on LSD, most cited first.

Study Year Design Participants
Neural correlates of the LSD experience revealed by multimodal neuroimaging. Human participants 2016 Experimental study
Crystal structure of an LSD-bound human serotonin receptor 2017 Experimental study with structural biology and molecular dynamics simulations
Lysergic Acid Diethylamide: Sensitive Neuronal Units in the Midbrain Raphe Midbrain neurons containing serotonin 1968 Experimental study
Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Human brain 2017 Experimental study
LSD-Assisted Psychotherapy in Patients with Terminal Cancer Cancer patients 1973 Experimental study n = 60

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