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

1. Octopamine (OA) (10(-7)-10(-5) M) relaxed isolated foreguts. Tyramine mimicked the effects of OA but was 64x less potent. 2. Proctolin (10(-8) M to 10(-6) M) induced contraction of isolated foreguts was antagonised non competitively by tyramine. 3. Mianserin (10(-6) M) was a non competitive antagonist of relaxation caused by tyramine but was without effect on proctolin induced contraction. 4. Caffeine (1 microM and 2 microM) caused non competitive inhibition of proctolin-induced tissue contraction. 5. It is concluded that tyramine antagonises proctolin-induced contraction of the foregut by activating an adenylate cyclase-linked OA2 receptor.
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PMID:Tyramine antagonizes proctolin-induced contraction of the isolated foregut of the locust Schistocerca gregaria by an interaction with octopamine2 receptors. 197 52

Receptors for biogenic amines such as dopamine, serotonin and epinephrine belong to the family of receptors that interact with G proteins and share a putative seven transmembrane domain structure. Using a strategy based on nucleotide sequence homology between the corresponding genes, we have isolated Drosophila cDNA clones encoding a new member of the G protein-coupled receptor family. This protein exhibits highest homology to the human alpha 2 adrenergic receptors, the human 5HT1A receptor and a recently cloned Drosophila serotonin receptor. The corresponding mRNA is found predominantly in adult Drosophila heads. Membranes from mammalian cells expressing this receptor displayed high affinity binding sites for [3H]yohimbine, an alpha 2 adrenergic receptor antagonist (Kd = 4.45 x 10(-9) M). Tyramine was the most efficient of the putative Drosophila neurotransmitters at displacing [3H]yohimbine binding (EC50 = 1.25 x 10(-6) M). Furthermore tyramine induced an inhibition of adenylate cyclase activity in NIH 3T3 cells expressing this receptor. The Drosophila tyramine receptor that we have isolated might therefore be an invertebrate equivalent of the mammalian alpha 2 adrenergic receptors.
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PMID:Cloning and characterization of a Drosophila tyramine receptor. 217 Jan 18

Adenylate cyclase in Drosophila melanogaster heads is stimulated 5-6-fold by low concentrations of octopamine. The octopamine stimulation is inhibited by low concentrations of the alpha-adrenergic ligands phentolamine and dihydroergotamine and of chlorpromazine, but not by low concentrations of the beta-antagonist propranolol and by the alpha-antagonist yohimbine. d-Tubocurarine enhances the octopamine effect. Tyramine, norepinephrine, and epinephrine also stimulate the cyclase, probably via the octopamine receptor. Serotonin and dopamine stimulate Drosophila adenylate cyclase 1.3-1.4-fold; at least the latter putative neurotransmitter seems to interact with a receptor distinct from the octopamine receptor. Prolonged incubation with dopamine in vitro abolishes adenylate cyclase basal activity as well as responsiveness to guanyl nucleotides, NaF, and putative neurotransmitters.
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PMID:Aminergic receptors in Drosophila melanogaster: responsiveness of adenylate cyclase to putative neurotransmitters. 612 19

The effects of dopamine (DA) on the smooth muscle fibres of the renal vascular bed are complex. They involve the postsynaptic alpha- and beta-adrenoceptors as well as the dopamine ones. On denervated kidney, in presence of alpha- and beta-blockers, intrarenal DA perfusion provokes vasodilation, increases natriuresis and stimulates renin secretion. The vasodilator effect of DA on the renal vascular bed was studied thanks to an isolated perfused rat kidney preparation which, when high concentrations of phenoxybenzamine and sotalol were present, made it possible to measure the effect of dopaminomimetics and dopaminolytics on the renal vascular resistance of a kidney previously vasoconstricted by continuous PGF2 alpha perfusion. (+)--Butaclamol and cis-flupenthixol proved to be invaluable tools to demonstrate the specificity of the dopamino-agonists response, since both shift the dose-response curve according to the criteria for competitive antagonism at doses at which their isomers are not active (fig. 2). Thus, it was possible to calculate the apparent pA2 for the various dopaminolytics and to classify them according to their affinity for the renal vascular dopamine receptors. Table 1 gives the classification. Flupenthixol, which has only a low affinity for the alpha 2-adrenoceptors, already inhibits the vasodilator effect of DA at 10(-8) M. The low stereospecificity of the enantiomers of sulpiride allows a distinction to be drawn between the "postsynaptic" vascular dopamine receptors and the presynaptic ones. The agonists of the renal vascular dopamine receptors provoked dose-dependent renal vasodilation on our preparation when phenoxybenzamine and sotalol were present and this was stereoselectively inhibited by (+)-butaclamol. Table II shows the activity of the dopaminomimetics meeting these criteria. p-Tyramine, di-propyl-m-tyramine and RU 24926 proved to have no dopaminomimetic effect. Their lack of activity seems to be attributable to the suppression of the hydroxyl in position 4. Mesenteric, splenic or cerebral artery preparations were also used to characterize the vascular dopamine receptors : tables III and IV compare the results taken from the literature. The classification obtained tallies quite well which suggests that the dopamine receptors located in the various vascular beds are identical. We compared the characteristics of the renal vascular dopamine receptor established from isolated rat kidney, with three other pharmacological models of dopamine receptor : the activation of dopamine-sensitive adenylate cyclase, the presynaptic modulation of the transmission of the sympathetic influx, and prolactin release (Table V).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pharmacologic characteristics of renal dopaminergic receptors: therapeutic perspectives]. 636 99

Earlier experiments only revealed involvement of sympathetic pre-synaptic dopaminergic receptors in dopamine induced inotropism in myocardium. We therefore used electrically stimulated (1 Hz) isolated 7-day-old chick embryo heart ventricles, thought to be devoid of functional sympathetic nerves, to re-investigate post-synaptic receptors involvement and particularly that of dopaminergic receptors in the positive inotropic effect of dopamine. The results showed that noradrenaline, isoprenaline and dopamine produced a positive inotropic effect with a similar efficacy and with an order of potency as follows: Isoprenaline = Noradrenaline > Dopamine. Tyramine induced no significant modification of the "initial tension" indicating that functional sympathetic innervation and/or releasable endogenous catecholamines were not demonstrable in the 7-day-old chick embryo heart ventricle. Propranolol (1 microM) competitively antagonized the positive inotropic response to isoprenaline, noradrenaline and dopamine, meanwhile phentolamine (3 microM) failed to significantly modify the effects of both noradrenaline and dopamine, indicating that these catecholamines induced their positive inotropic effects via stimulation of beta-adrenoceptors; involvement of alpha-adrenergic receptors stimulation was not demonstrable in these effects. Moreover, haloperidol (2 microM) antagonized the positive inotropic response to dopamine but had not any significant effect on the response to isoprenaline. The combined application of both propranolol and haloperidol antagonized the positive inotropic response to dopamine to a greater extent than when these two antagonists were given alone. Consequently, post-synaptic dopaminergic receptors were also involved in the positive inotropic effect of dopamine. Furthermore, in preparations in which sodium channels were inactivated by high potassium physiological salt solution, high concentrations of dopamine (0.1 mM to 1 mM) induced a slow developing electrical and positive inotropic responses which were also inhibited by propranolol and haloperidol, but not by phentolamine. These latter results indicated that like beta-adrenergic stimulation, the slow inward calcium current activated by stimulation of adenylate cyclase, was at least in part involved in the positive inotropic response to dopamine. In conclusion, dopamine induced its positive inotropism via stimulation of post-synaptic beta-adrenergic and dopaminergic receptors. The contribution of dopaminergic receptors in this positive inotropic effect might be of the DA-2 receptors since haloperidol used had been reported to be more DA-2 than DA-1 antagonist. These DA-2 receptors subtypes would mediate activation of adenylate cyclase.
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PMID:Receptors involved in the positive inotropic action induced by dopamine on the ventricle of a 7-day-old chick embryo heart. 956 66

A cDNA encoding a biogenic amine receptor (B96Bom) was isolated from silkworm (Bombyx mori) larvae, and the ligand response of the receptor stably expressed in HEK-293 cells was examined. Tyramine (TA) at 0.1-100 micro m reduced forskolin (10 micro m)-stimulated intracellular cAMP levels by approximately 40%. The inhibitory effect of TA at 1 micro m was abolished by yohimbine and chlorpromazine (each 10 micro m). Although octopamine (OA) also reduced the cAMP levels, the potency was at least two orders of magnitude lower than that of TA. Furthermore, unlabelled TA (IC50 = 5.2 nm) inhibited specific [3H]TA binding to the membranes of B96Bom-transfected HEK-293 cells more potently than did OA (IC50 = 1.4 micro m) and dopamine (IC50 = 1.7 micro m). Taken together with the result of phylogenetic analysis, these findings indicate that the B96Bom receptor is a B. mori TA receptor, which is negatively coupled to adenylate cyclase. The use of this expression system should facilitate physiological studies of TA receptors as well as structure-activity studies of TA receptor ligands.
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PMID:B96Bom encodes a Bombyx mori tyramine receptor negatively coupled to adenylate cyclase. 1275 54

In invertebrates, the biogenic-amine octopamine is an important physiological regulator. It controls and modulates neuronal development, circadian rhythm, locomotion, 'fight or flight' responses, as well as learning and memory. Octopamine mediates its effects by activation of different GTP-binding protein (G protein)-coupled receptor types, which induce either cAMP production or Ca(2+) release. Here we describe the functional characterization of two genes from Drosophila melanogaster that encode three octopamine receptors. The first gene (Dmoa1) codes for two polypeptides that are generated by alternative splicing. When heterologously expressed, both receptors cause oscillatory increases of the intracellular Ca(2+) concentration in response to applying nanomolar concentrations of octopamine. The second gene (Dmoa2) codes for a receptor that specifically activates adenylate cyclase and causes a rise of intracellular cAMP with an EC(50) of approximately 3 x 10(-8) m octopamine. Tyramine, the precursor of octopamine biosynthesis, activates all three receptors at > or = 100-fold higher concentrations, whereas dopamine and serotonin are non-effective. Developmental expression of Dmoa genes was assessed by RT-PCR. Overlapping but not identical expression patterns were observed for the individual transcripts. The genes characterized in this report encode unique receptors that display signature properties of native octopamine receptors.
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PMID:A family of octopamine [corrected] receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogaster. 1581 67