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 of the United States of America ·Vol. 71 ·No. 3 ·1974-03-00 ·Pages 797-801

Nathanson JA, Greengard P

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.

MeSH Terms

Adenylyl Cyclases/metabolism Animals Bromine/pharmacology Cockroaches Cyproheptadine/pharmacology Dopamine/pharmacology Enzyme Activation/drug effects Ganglia, Autonomic/enzymology,metabolism In Vitro Techniques Lysergic Acid Diethylamide/pharmacology Norepinephrine/pharmacology Octopamine/pharmacology Phentolamine/pharmacology Receptors, Drug Serotonin/metabolism,pharmacology Serotonin Antagonists Stimulation, Chemical

Chemicals

Receptors, Drug Serotonin Antagonists Octopamine Cyproheptadine Serotonin Lysergic Acid Diethylamide Adenylyl Cyclases Bromine Dopamine Norepinephrine Phentolamine

Authors & Affiliations

2 authors, click to expand affiliations / ORCID

Nathanson J A

Greengard P

References (18)

18 references, click to expand

The role of cyclic AMP in the control of fluid secretion.
Adv Cyclic Nucleotide Res. 1972;1:137-47 PMID: 4353163
Saturation assay for cyclic AMP using endogenous binding protein.
Adv Cyclic Nucleotide Res. 1972;2:25-40 PMID: 4352294
Relationships of psychotomimetic to anti-serotonin potencies of congeners of lysergic acid diethylamide (LSD-25).
Psychopharmacologia. 1959;1:20-8 PMID: 14405872
Mode of action of hallucinogenic molecules.
Nat New Biol. 1973 Jun 27;243(130):283-4 PMID: 4352120
Direct postsynaptic responses to stimulation of serotonin-containing neurones.
Nature. 1970 Mar 14;225(5237):1060-2 PMID: 5416479
Dopamine-sensitive adenylate cyclase in caudate nucleus of rat brain, and its similarity to the "dopamine receptor".
Proc Natl Acad Sci U S A. 1972 Aug;69(8):2145-9 PMID: 4403305
Cyclic adenosine monophosphate in the nervous system of Aplysia californica. II. Effect of serotonin and dopamine.
J Gen Physiol. 1972 Nov;60(5):570-87 PMID: 4345440
The effect of serotonin (5-hydroxytryptamine) on the formation of adenosine 3',5'-phosphate by tissue particles from the liver fluke, Fasciola hepatica.
J Biol Chem. 1960 Feb;235:466-70 PMID: 14420764
The distribution and metabolism of lysergic acid diethylamide.
Ann N Y Acad Sci. 1957 Mar 14;66(3):435-44 PMID: 13425233
Octopamine-sensitive adenylate cyclse: evidence for a biological role of octopamine in nervous tissue.
Science. 1973 Apr 20;180(4083):308-10 PMID: 4349510
Cyclic AMP-mediated adrenergic synapses to cerebellar Purkinje cells.
Adv Cyclic Nucleotide Res. 1972;1:411-23 PMID: 4353180
Effects of hallucinogenic and tranquilizing drugs on serotonin evoked uterine contractions.
Proc Soc Exp Biol Med. 1956 Jan;91(1):39-41 PMID: 13297703
Neuronal responses to 5-hydroxytryptamine resulting from membrane permeability decreases.
Nat New Biol. 1973 Aug 8;244(136):171-3 PMID: 4516447
Serotonin: two different inhibitory actions on snail neurons.
Science. 1971 Mar 26;171(3977):1252-4 PMID: 5545203
Some serotoninlike activities of lysergic acid diethylamide.
Science. 1956 Jul 20;124(3212):121-2 PMID: 13337360
Binding of d-lysergic acid diethylamide to subcellular fractions from rat brain.
Nature. 1972 May 19;237(5351):164-6 PMID: 4555508
The influence of chemical agents on the accumulation of adenosine 3',5'-Phosphate in slices of rabbit cerebellum.
Mol Pharmacol. 1968 Jul;4(4):367-78 PMID: 4298780
Comparative study on the serotonin antagonism of amide derivatives of lysergic acid and of ergot alkaloids.
J Pharmacol Exp Ther. 1958 Jan;122(1):124-36 PMID: 13502837

Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.71.3.797

Published

1974-03-00

Pages

797-801

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC388101

Subset

External Links

PubMed source DOI: 10.1073/pnas.71.3.797 PMC Full Text View journal details

Analysis Services

Serotonin-sensitive adenylate cyclase in neural tissue and its similarity to the serotonin receptor: a possible site of action of lysergic acid diethylamide.

Contact

WeChat Official Account