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 via OpenAlex
Summary
AI-generated from the abstractAn enzyme called adenylate cyclase, found in the thoracic ganglia of an insect nervous system, is specifically activated by low concentrations of serotonin. This activation is selectively blocked by very low concentrations of D-lysergic acid diethylamide (LSD), 2-bromo-LSD, and cyproheptadine, substances known to block certain serotonin receptors in living organisms. The inhibition is competitive with respect to serotonin, and the inhibitory constant of LSD for this serotonin-sensitive adenylate cyclase is 5 nM. These findings suggest that the serotonin receptor in neural tissue is closely linked to this enzyme, which may mediate serotonergic neurotransmission, and that some physiological effects of LSD might occur through interaction with this enzyme.
Study at a glance
| 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 |
| Citations | 95 |
| Key finding | 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.