Serotonin-Sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide
Proceedings of the National Academy of Sciences – March 01, 1974
Source: OpenAlex
Summary
Low concentrations of serotonin activate a specific adenylate cyclase in insect nervous systems, crucial for neurotransmission. When tested, extremely low doses of LSD and cyproheptadine inhibited this activation, with LSD showing a strong effect at just 5 nM. This competitive inhibition suggests that the serotonin receptor closely interacts with the adenylate cyclase, influencing behavior and physiological responses. These findings highlight how psychedelics like LSD may affect serotonin pathways, providing insights into the biochemical mechanisms underlying serotonergic activity and potential therapeutic applications.
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.