Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serotonin (5-hydroxytryptamine, 5-HT) inhibited the formation of cAMP promoted by vasoactive intestinal polypeptide, plus forskolin, in mouse hippocampal and cortical neurons in primary culture. The rank order of potencies of classical 5-HT1 agonists in inhibiting cAMP formation in hippocampal neurons was 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) greater than 5-carboxamidotryptamine (5-CT) greater than d-lysergic acid diethylamide greater than 5-HT greater than 5-methoxy-N,N-dimethyltryptamine (5-MeO-N,N-DMT) greater than RU 24969 greater than ipsapirone greater than bufotenine greater than buspirone [half-maximal efficacy (EC50) = 7, 18, 30, 52, 90, 102, 100, 110, and 128 nM, respectively]. All the tryptamine derivatives substituted in position 5 of the indol were potent agonists [5-HT, 5-CT, 5-MeO-N,N-DMT, 5-methoxytryptamine, and bufotenine], whereas tryptamine, N-methyltryptamine, and N,N-dimethyltryptamine were poor agonists. The most potent antagonists tested were spiperone, (+/-)-pindolol, (+/-)-cyanopindolol, WB4101, and methiothepin, the affinity of spiperone for this receptor being 22 nM. In contrast, ketanserin, a specific 5-HT2 antagonist, and 5-HT3-selective drugs (ICS 205 930 and MDL 72222) were very weak in antagonizing the 5-HT-inhibited cAMP formation. The pharmacological profiles of 5-HT receptors mediating the inhibition of cAMP formation indicate that these receptors correspond to the 5-HT1A-binding site subtypes. Experiments with the Bordetella pertussis toxin indicate that the 5-HT1A receptor mediating inhibition of cAMP production involves a pertussis toxin-sensitive GTP-binding protein. In the absence of VIP, cAMP formation could be stimulated through a 5-HT receptor, but the specific 5-HT1A agonists, 8-OH-DPAT and RU 24969 did not stimulate cAMP production. These results suggest that in mouse embryonic hippocampal neurons, the 5-HT1A receptors, which are negatively coupled to adenylate cyclase, are distinct from the receptor positively coupled to this enzyme. The pharmacological characterization of the 5-HT receptor negatively coupled to adenylate cyclase in mouse embryonic cortical neurons indicates that it differs from the 5-HT1A receptor found in hippocampal neurons. Its main differences with the 5-HT1A receptor in hippocampal neurons are as follows: 1) 8-OH-DPAT was only a poor partial agonist in cortical neurons, whereas it was the best full agonist in hippocampal neurons; and 2) metergoline and methysergide as well as the anxiolytic drugs, ipsapirone and buspirone, which were potent agonists in hippocampal neurons, were competitive antagonists in cortical neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Pharmacology of 5-hydroxytryptamine-1A receptors which inhibit cAMP production in hippocampal and cortical neurons in primary culture. 282 13

A nonclassical 5-hydroxytryptamine (5-HT) receptor mediates the stimulation of adenylate cyclase activity in mouse embryo colliculi neurons in primary culture. The pharmacological profile characterized with agonists and antagonists suggests that this 5-HT receptor does not appear to correspond to a known 5-HT receptor. On this 5-HT receptor, 5-HT (EC50 = 109 +/- 17 nM) and 5-methoxytryptamine (5-MeOT) were equipotent agonists. The other tryptamine derivatives, 5-carboxamidotryptamine (5-CT) and 5-methoxy-N,N-dimethyltryptamine (5-MeOT-N,N-DMT), were full potent agonists, whereas tryptamine, bufotenine, and 2-CH3-5-HT were weak partial agonists. Two selective 5-HT1A agonists: 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and ipsapirone, could not stimulate adenylate cyclase. RU 24969, a tetrahydropyridoindole derivative that is a potent 5-HT1A and 5-HT1B agonist was also inactive, whereas RU 28253, another member of this series, could stimulate cAMP production. The action of antagonists acting on 5-HT1 or 5-HT2 receptors, such as methiothepin (5-HT1 and 5-HT2), metergoline (5-HT1 and 5-HT2), spiperone (5-HT1A and 5-HT2), (-)-pindolol (5-HT1B), mesulergine (5-HT1C), and ketanserin (5-HT2), were almost inactive in reversing the 5-HT stimulating effect. The selective 5-HT3 antagonist ICS 205 930 was a full competitive antagonist at this receptor. Nevertheless, MDL 72222, which is also a 5-HT3 antagonist, was very weak in antagonizing the 5-HT stimulatory effect. A receptor with similar characteristics has also been found in guinea pig hippocampal membranes. In these membranes, the second receptor of low affinity for 5-HT, termed RL, which is positively coupled to adenylate cyclase, was also antagonized by ICS 205 930. The relatively low affinity of this hippocampal receptor for 5-CT, its stimulation by RU 28253 but not by RU 24969, and its previously reported pharmacological characteristics support the contention that this 5-HT receptor and the 5-HT receptor of mouse embryo colliculi neurons in primary culture (both positively coupled to cAMP formation) present great homologies. Inasmuch as none of the classical specific 5-HT1 and 5-HT2 agonists or antagonists interact with these 5-HT receptors, it is unlikely that they belong to 5-HT1 or 5-HT2 receptor categories.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. 284 52

Glial cell membrane fractions were prepared using glial cells preparations isolated from horse brain striatum. [3H]5-HT binding was measured by the filtration technique and the adenylate cyclase activity determined by measuring the cAMP production using a radioimmunoassay. Serotonin binds to glial membrane fractions with an affinity corresponding to a dissociation constant Kd = nM. The corresponding site is serotoninergic specific: [3H]5-HT binding is inhibited by 5-HT agonists (5 OH NM-DMT, 5-MeOHT, 5-MeOH-DMT, NN-DMT) or antagonists (cinanserine, cyproheptadine, methysergide, LSD) and not (or poorly) inhibited by non-serotoninergic related drugs. The population of sites binding 5-HT, present in neuronal membrane preparations and determined in parallel assays is distinct from that observed in glial preparations. The glial membrane fractions contains an adenylate cyclase activated by 5-HT with an apparent affinity constant close to 1 microM. It is serotonin-specific and clearly distinct from the DA-stimulated adenylate cyclase present in the same preparation. The sites binding 5-HT and activating the adenylate cyclase with low affinities might be directly related. This system, clearly distinct from the postsynaptosomal serotoninergic receptor, represents presumably a glial serotoninergic receptor; however, it cannot be totally excluded that these sites may refer to presynaptic membranes.
 ...
PMID:[3H]5-HT binding sites and 5-HT-sensitive adenylate cyclase in glial cell membrane fraction. 740 3

N-Benzenesulfonyl-5-methoxy-N,N-dimethyltryptamine (BS/5-OMe DMT; 5) was shown to bind at human 5-HT6 serotonin receptors with high affinity (Ki = 2.3 nM) relative to serotonin (Ki = 78 nM). Structural variation failed to result in significantly enhanced affinity. BS/5-OMe DMT acts as an antagonist of 5-HT-stimulated adenylate cyclase (pA2 = 8.88 nM) and may represent the first member of a novel class of 5-HT6 antagonists.
 ...
PMID:N1-(Benzenesulfonyl)tryptamines as novel 5-HT6 antagonists. 1105 42