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)

1. HT-90B ((-)-N-([2-(8-methyl-l, 4-benzodioxane-2-ylmethyl)amino]ethyl) tricyclo[3,3,1,1(3.7)] decane-1-carboxamide) had high affinities for the 5-HT1A (Ki = 0.18 nM) and 5-HT2 (Ki = 9.2 nM) receptors. 2. HT-90B inhibited forskolin activated adenylate cyclase in rat hippocampal membranes as a 5-HT1A full agonist (IC50 = 2 nM), and the potency of the drug was higher than that of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a standard 5-HT1A agonist. 3. In the serotonin syndrome test, HT-90B behaved as a weak partial 5-HT1A agonist in reserpinized rats. 4. 5-HT2 receptor-mediated potentiation of rabbit platelet aggregation by serotonin (5-HT) was reduced by HT-90B (IC50 = 1.73 microM). 5. Head twitch response induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a 5-HT2 agonist, was inhibited by HT-90B in mice. 6. It is concluded that HT-90B has potent 5-HT1A receptor agonist as well as 5-HT2 receptor antagonist properties in vitro and in vivo.
 ...
PMID:Pharmacological profile of (-)HT-90B, a novel 5-HT1A receptor agonist/5-HT2 receptor antagonist. 878 43

1. Isolated cannulated ventricles commenced spontaneous beating on application of perfusion pressure of 10 cm water. Complete hearts showed a fast patterned cyclical rhythm, whereas ventricles devoid of atrial material showed a continuous slow rhythm. 2. Perfused ventricles were inhibited by ACh with a threshold at 10(-8) mol l-1 and arrested at 10(-7) mol l-1, and ventricles under stimulation by 5HT could be arrested by ACh at this concentration. 3. Perfused ventricles were stimulated by 5HT, with threshold at 10(-9) mol l-1 and maximum at 10(-5) mol l-1. Metoclopramide was without affect on 5HT responses, but metitipine and methysergide did inhibit such responses suggesting that the 5HT receptor present possessed mixed properties of the vertebrate 5-HT1 and 5-HT2 receptor subtypes. 4. Ventricles were very sensitive to the excitatory actions of FMRFamide in the 10(-9) to 10(-5) mol l-1 range. Preparations were insensitive to GAPFLRFamide, but SCP-B was modestly excitatory (threshold 10(-7) mol l-1). 5. Preparations were not significantly affected by adenosine, ATP, and guanosine, but GTP was strongly excitatory at 10(-7) mol l-1. 6. 5HT and FMRFamide responses were additive. Preparations responded strongly to the adenylate cyclase activator forskolin and dibutyryl cAMP enhanced spontaneous contractions and 5HT responses, suggesting that the 5HT receptor may operate via a cAMP secondary mechanism. 7. The IP3 inhibitor lithium (10 mmol l-1), caused slight inhibition of FMRFamide responses, suggesting that the receptor to this peptide may operate via IP3 as a second messenger. 8. Neuromodulation in this preparation would appear to involve ACh as inhibitor, 5HT and FMRFamide as upregulators, with no clear roles for FMRFamide-related peptides and GTP.
 ...
PMID:Modulatory mechanisms in the isolated internally perfused ventricle of the whelk Busycon canaliculatum. 884 83

1. 5-Hydroxytryptamine (5-HT) exerts both contractile and relaxant effects in the marmoset isolated aorta, actions that are unaffected by the 5-HT2 antagonist ketanserin. The aim of the present study was to define the receptors mediating the contractile activity of 5-HT in the marmoset aorta. 2. Contractile responses were elicited in aortic rings that were either: (i) precontracted submaximally with the thromboxane A2 agonist U44069 in order to amplify the responses; or (ii) exposed to N(omega)-nitro-L-arginine (100 micromol/L) plus LY 53857 (0.1 micromol/L; a 5-HT2 receptor antagonist shown previously to inhibit relaxation). The effect of 5-HT on adenosine 3',5'-cyclic monophosphate (cAMP) formation was also investigated. 3. The effects of agonists and antagonists comprised: (i) agonist potencies in the order 5-carboxamidotryptamine > 5-HT > sumatriptan > 8-hydroxy-2-(di-n-propylamino)tetralin; (ii) inhibition of contractile action of 5-HT by the 5-HT1D antagonist GR 127935; (iii) a contractile response to methysergide; (iv) a lack of effect of tropisetron, an antagonist of 5-HT3 and 5-HT4 receptors; and (v) inhibition of forskolin-stimulated cAMP formation by 5-HT (in the presence of LY 53857), indicative of negative coupling to adenylate cyclase. 4. The above effects fulfill the criteria for a 5-HT1-like receptor. In view of the previous finding that this contractile response is insensitive to ketanserin, it is concluded that the contractile effects of 5-HT in the marmoset aorta are mediated exclusively by a 5-HT1-like receptor.
 ...
PMID:5-Hydroxytryptamine-induced contraction of the marmoset aorta is mediated by a 5-HT1-like receptor. 959 May 77

Serotonin (5-HT) receptors play key regulatory roles in nematodes and alternatively spliced 5-HT2 receptor isoforms have been identified in the parasitic nematode, Ascaris suum. 5-HT2As1 and 5-HT2As2 contain different C-termini, and 5-HT2As1Delta4 lacks 42 amino acids at the C-terminus of the third intracellular loop. 5-HT2As1 and 5-HT2As2 exhibited identical pharmacological profiles when stably expressed in human embryonic kidney (HEK) 293 cells. Both 5-HT2As isoforms had higher affinity for 5-HT than their closely related Caenorhabditis elegans homolog (5-HT2Ce). This increased 5-HT affinity was not related to the substitution in 5-HT2As1 of F120 for Y in the highly conserved DRY motif found in the second intracellular loop of other 5-HT receptors, since a 5-HT2As1F120Y mutant actually exhibited increased 5-HT affinity compared with that of 5-HT2As1. As predicted, cells expressing either 5-HT2As1 or 5-HT2As2 exhibited a 5-HT-dependent increase in phosphatidylinositol (PI) turnover. In contrast, although 5-HT2As1Delta4 displayed a 10-fold higher affinity for 5-HT and 5-HT agonists than either 5-HT2As1 or 5-HT2As2, 5-HT2As1Delta4 did not couple to either PI turnover or adenyl cyclase activity. Based on RT-PCR, 5-HT2As1 and 5-HT2As2 were more highly expressed in pharynx and body wall muscle and 5-HT2As1Delta4 in nerve cord/hypodermis. This is the first report of different alternatively spliced 5-HT2 receptor isoforms from any system.
 ...
PMID:Functional characterization of alternatively spliced 5-HT2 receptor isoforms from the pharynx and muscle of the parasitic nematode, Ascaris suum. 1242 36


<< Previous 1 2