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Nathanson IA, Greengard P. 
“Serotonin-sensitive Adenylate Cyclase in Neural Tissue and Its Similarity to the Serotonin Receptor: A Possible Site of Action of Lysergic Acid Diethylamide.”. 
Proc Natl Acad Sci. 1974;71(3):797- 801.
The pharmacological properties of a serotonin-sensitive adenylate cyclase (AC) found in the nervous tissue of insects were investigated. Methods Pro- mesa- and metathoracic ganglia from adult cockroaches (Periplaneta americana) were homogenized and AC activity measured by the rate of formation of cyclic AMP from ATE. AC Activity measured in the presence of added test substancels) was expressed as a 0f control activity (no added test substance). Results Serotonin (5-HT) 2.5 x 10 6M stimulated ganglionic AC to 1637 of control. This stimulation was reduced by 50% with LSD 2 x 10-8 M and almost abolished with LSD I x 10-7 M. LSD at >1 x l 0 6M stimulated AC activity in the absence or presence of 5-HT. LSD At 1.25 x 10 -5 M increased AC activity to 2100f controls in the presence or absence of 2.5 x 10 6 5-HT. Stimulation of AC by dopamine 2.5 x 10 6M, octopamine 2.5 x 10 6M and norepinephrine 5 x 10 5M was not inhibited by low concentrations of LSD (10 5 x 10 -6M). 5-HT Antagonists 2-bromo-LSD (BOL) 1 x 1O-8M and cyproheptadine (Merek-USA) 2 x Io-7M inhibited 5-HT stimulation of AC activity by 50% and to a much less extent that; by dopamine, octamine or norepinephrine. BOL Alone in higher concentrations (i x 10 6M or more) stimulated AC activity, but cyproheptadine depressed basal levels even in the presence of 5-HT Both LSD and BOL produced a shift to the right in the dose-response curve, increasing Ma but not Vmax. and indicating competitive inhibition. Phentolamine competitively inhibited 5-HT octopamine dopamine and norepinephrine stimulated adenylate cyclase activity. Its inhibition of 5-HT action was less effective than that of the other putative neurotransmitters. Conclusion The 5-HT receptor in neural tissue may be associated with a 5-HT-sensitive AC-mediated serotonergic transmission, and this system may be involved in the physiological actions of LSD.
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