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PubMed1999

Prolonged negative selection of Drosophila melanogaster for a character of adaptive significance disturbs stress reactivity.

The metabolism of juvenile hormone by JH-esterase and JH-epoxide hydrolase, and octopamine by tyrosine decarboxylase were studied under normal and stress conditions in flies of two related lines of D. melanogaster. One was selected for high (HA line) and another for low (LA line) male sexual activity for more than 700 generations. It was demonstrated that prolonged selection for low male sexual activity results in considerable changes in both systems. Tyrosine decarboxylase activity in males and females of the LA line was sharply reduced as compared with those of the HA and control Canton-S lines; JH-esterase and JH-epoxide hydrolase activities were decreased in females, and not in males, of the LA line. It was demonstrated that the response of both metabolic systems to heat stress is impaired in individuals of the LA line: the system of juvenile hormone metabolism does not respond to stress, and that of octopamine metabolism is decelerated. The role of juvenile hormone metabolism in male reproductive function is discussed.

Adaptation, Biological↗
PubMed2000

Electrophysiological responses of crayfish oocytes to biogenic amines.

Intracellular recordings were made from immature, growing oocytes of the crayfish Pacifastacus leniusciulus. Oocytes had a relatively negative resting potential of -74.7+/-2.2 mV (n=26; range -53 to -90) and a mean input resistance of 0.86+/-0.19 MOmega (n=22; range 0.17-3.3). Octopamine induced a long-lasting response involving biphasic changes in input resistance, together with bi- or multiphasic changes in membrane potential. The resistance-decreasing phase involved (in different oocytes) membrane hyperpolarization, depolarization or both. The resistance-increasing phase was usually a depolarization. The hyperpolarizing form of the resistance-decreasing response, and the depolarizing resistance-increasing response reversed in polarity at membrane potentials of (respectively) -90 and -92 mV, suggesting increases and decreases in K(+) conductance underly the biphasic changes in input resistance. The threshold concentration for the response was remarkably low (>10(-12) M) and showed little or no dose-dependence over the concentration range 10(-12)-10(-6) M. Similar responses were evoked by dopamine and serotonin (at 10(-9) M), although a higher proportion of oocytes responded to octopamine and/or dopamine than to serotonin.

Animals↗
PubMed2001

Insecticidal activity of essential oils: octopaminergic sites of action.

UNLABELLED: A study was conducted to determine the insecticidal activity and mechanism of action of three essential oils (eugenol, alpha-terpineol and cinnamic alcohol) and an equal part mixture (3-blend) against American cockroaches (Periplaneta americana). To address species differences in response to treatment with the test oils, Carpenter ants (Camponotus pennsylvanicus De Geer), and German cockroaches (Blattella germanica) were included in this study. Exposed American cockroaches demonstrated hyperactivity followed by hyperextension of the legs and abdomen, then fast knockdown or quick immobilization followed by death. Ants and German cockroaches showed fast immobilization/knockdown followed by mortality. The 1:1:1 mixture (3-blend) was substantially effective against all test insects. One of the most remarkable observations was the increased frequency of heartbeats of American cockroaches in response to topical application of test oils. The changes in the pattern of cAMP level was biphasic. A significant increase in the cAMP level was found in response to 1 nmol/ml of eugenol, or 3-blend or 10 nmol/ml of alpha-terpineol. At higher concentrations a significant decrease in cAMP level was found. Blockage of octopamine receptors binding sites was also illustrated at lower concentrations of the test chemicals as judged by the decreased binding activity of [3H]octopamine to its receptors. IN CONCLUSION: (1) test oils are neuro-insecticides and their insecticidal activity is species-dependent; (2) a synergistic effect of the three oils was found when they were equally mixed (3-blend); and (3) the octpaminergic system mediates the insecticidal activity of eugenol, alpha-terpienol and the 3-blend.

Administration, Topical↗
PubMed2003

In vitro expression and pharmacology of the 5-HT7-like receptor present in the mosquito Aedes aegypti tracheolar cells and hindgut-associated nerves.

We have previously reported the cloning of a 5-hydroxytryptamine receptor (Aedes 5-HT7-like receptor) from adult Aedes aegypti. For functional expression of the Aedes 5-HT7-like receptor, CHO-K1 cells were stably transfected with a receptor expression construct, pC5-HT7. The Aedes 5-HT7-like receptor positively coupled to Gs protein, increasing intracellular cAMP in response to 5-HT; adenylyl cyclase activity was induced in a concentration-dependent, saturable manner. Only 5-HT, and not octopamine, dopamine or tyramine, caused the induction of cAMP. At 10 nM 5-HT a weak synergism was observed between octopamine and 5-HT. Other known agonists of the mammalian 5-HT7 receptor were tested. Their order of potency was: 5-HT >> 5-CT = 8-OH-DPAT >> pimozide. This is the first report on the functional expression of a mosquito neurohormone receptor.

Adenylyl Cyclases↗
PubMed2000

Amtyr1: characterization of a gene from honeybee (Apis mellifera) brain encoding a functional tyramine receptor.

Biogenic amine receptors are involved in the regulation and modulation of various physiological and behavioral processes in both vertebrates and invertebrates. We have cloned a member of this gene family from the CNS of the honeybee, Apis mellifera. The deduced amino acid sequence is homologous to tyramine receptors cloned from Locusta migratoria and Drosophila melanogaster as well as to an octopamine receptor cloned from Heliothis virescens. Functional properties of the honeybee receptor were studied in stably transfected human embryonic kidney 293 cells. Tyramine reduced forskolin-induced cyclic AMP production in a dose-dependent manner with an EC50 of approximately 130 nM. A similar effect of tyramine was observed in membrane homogenates of honeybee brains. Octopamine also reduced cyclic AMP production in the transfected cell line but was both less potent (EC50 of approximately 3 microM) and less efficacious than tyramine. Receptor-encoding mRNA has a wide-spread distribution in the brain and subesophageal ganglion of the honeybee, suggesting that this tyramine receptor is involved in sensory signal processing as well as in higher-order brain functions.

Amino Acid Sequence↗
PubMed2002

Characterization of a tyramine receptor from Caenorhabditis elegans.

Octopamine (OA) plays an important role in the regulation of a number of key processes in nematodes, including pharyngeal pumping, locomotion and egg-laying. However, while putative OA receptors can be tentatively identified in the Caenorhabditis elegans database, no OA receptors have been functionally characterized from any nematode. We have isolated two cDNAs, ser-2 and ser-2a, encoding putative C.elegans serotonin/OA receptors (C02D4.2, ser-2). The sequences of these cDNAs differ from that predicted by GeneFinder and lack 42 bp of exon 2. In addition, ser-2a appears to be alternatively spliced and lacks a predicted 23 amino acids in the third intracellular loop. COS-7 cells expressing SER-2 bind [3H]LSD in the low nM range and exhibit Kis for tyramine, octopamine and serotonin of 0.07, 2, and 13.7 micro m, respectively. Significantly, tyramine reduces forskolin-stimulated cAMP levels in HEK293 cells stably expressing SER-2 with an IC50 of about 360 nm, suggesting that SER-2 is a tyramine receptor.

Amino Acid Sequence↗
PubMed1991

Innervation and neural regulation of the sex pheromone gland in female Heliothis moths.

Female Heliothis moths normally produce their species-specific male attractant (sex pheromone blend) during scotophase, and this production is stimulated by pheromone biosynthesis activating neuropeptide (PBAN), presumably carried in the hemolymph. Several lines of evidence indicate that the central nervous system plays another critical role in this regulation. Pheromone biosynthesis was induced during photophase by electrical stimulation of the ventral nerve cord or the peripheral nerves projecting from the terminal abdominal ganglion to the pheromone gland in the tip of the abdomen. Electron microscopy further revealed that axonal branches innervate the gland tissue. Nerve branches associated with pheromone gland cells are enwrapped in glia and contain dense-core vesicles, suggesting that the innervation of the gland might be neurosecretory. Finally, the biogenic monoamine octopamine was nearly as effective as purified Heliothis zea PBAN in stimulating pheromone biosynthesis when injected into intact females during mid-photophase. Furthermore, both octopamine and PBAN stimulated significant increases in the pheromone content of the glands in isolated abdomens lacking a ventral nerve cord but only when abdomens were treated at the onset of scotophase. These data suggest that the regulation of sex pheromone production in Heliothis is more complex than previously thought. Activation of the gland appears to be governed by both neural and hormonal mechanisms, and these control mechanisms depend on photoperiodic cues.

Animals↗
PubMed2003

Inhibitors of calling behavior of Plodia interpunctella.

Some octopamine agonists were found to suppress the calling behavior of the stored product Indian meal moth, Plodia interpunctella. Compounds were screened using a calling behavior bioassay using female P. interpunctella. Four active derivatives, with inhibitory activity at the nanomolar range, were identified in order of decreasing activity: 2-(1-phenylethylamino)-2-oxazoline > 2-(2-ethyl,6-methylanilino)oxazolidine > 2-(2-methyl benzylamino)-2-thiazoline > 2-(2,6-diethylanilino)thiazolidine. Three-dimensional pharmacophore hypotheses were built from a set of 15 compounds. Among the ten common-featured models generated by the program Catalyst/HipHop, a hypothesis including a hydrogen-bond acceptor lipid, a hydrophobic aromatic and two hydrophobic aliphatic features was considered to be essential for inhibitory activity in the calling behavior. Active compounds mapped well onto all the hydrogen-bond acceptor lipid, hydrophobic aromatic and hydrophobic aliphatic features of the hypothesis. On the other hand, less active compounds were shown not to achieve the energetically favorable conformation that is found in the active molecules in order to fit the 3D common-feature pharmacophore models. The present studies demonstrate that inhibition of calling behavior is via an octopamine receptor.

Adrenergic alpha-Agonists↗
PubMed2006

Abnormal platelet trace amine profiles in migraine with and without aura.

Trace amines, including tyramine, octopamine and synephrine, are closely related to classic biogenic amines. In one study, where these substances were found elevated in plasma of migraineurs, it was hypothesized that trace amine metabolism is deranged in migraine. To confirm these findings, we studied, using a multichannel electrochemical high-performance liquid chromatography system, the concentrations of trace amines in platelets of migraine without aura (MoA) and migraine with aura (MA) patients in headache-free period, compared with controls. Platelet concentrations of trace amines, although elevated in both migraine types, showed a different profile in MoA and MA. Octopamine was significantly higher in MoA sufferers (0.69 +/- 0.43 ng/10(8) platelets) compared with both control subjects (0.22 +/- 0.16 ng/10(8) platelets) and MA patients (0.39 +/- 0.37 ng/10(8) platelets). Synephrine was significantly higher in MA patients (0.72 +/- 0.44 ng/10(8) platelets) with respect to both controls (0.33 +/- 0.25 ng/10(8) platelets) and MoA sufferers (0.37 +/- 0.29 ng/10(8) platelets). These results strengthen the hypothesis that tyrosine metabolism is deranged in migraine and may participate in its pathophysiology.

Adolescent↗
PubMed1981

Biosynthesis of N-acetyldopamine and N-acetyloctopamine by Schistocerca gregaria nervous tissue.

N-Acetyltyramine, N-acetyldopamine and N-acetyloctopamine were the major products when either L-[3H]tyrosine or [3H]tyramine were incubated with thoracic ganglia of the desert locust, Schistocerca gregaria. No label was incorporated into L-DOPA under these conditions, although 2-3% of the radioactivity could be recovered in dopamine and octopamine. Addition of the aromatic amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine (NSD 1015), prevented the formation of N-acetylcompounds from L-[3H]tyrosine, without resulting in an accumulation of label in L-DOPA. In contrast, incubation of samples of haemolymph with L-[3H]tyrosine resulted in the recovery of 7% of label in L-DOPA, which was increased to 17% in the presence of NSD 1015. These results provide evidence that the initial step in the synthesis of dopamine and octopamine by S. gregaria nervous tissue is the conversion of L-tyrosine to tyramine, which is subsequently metabolised to N-acetyltyramine, N-acetyldopamine or N-acetyloctopamine.

Animals↗
PubMed2004

Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators.

The presence of the so-called trace amines 2-phenylethylamine, m-tyramine, p-tyramine, m-octopamine, p-octopamine and tryptamine in the mammalian central nervous system has been known for several decades. Despite much initial interest, these amines have largely been thought of as little more than metabolic by-products. The recent description of a family of mammalian trace amine receptors has, however, seen a resurgence of interest in the physiological role of this class of compounds. Although the trace amines are well documented to cause amphetamine-like effects, such responses only occur at concentrations multiple orders of magnitude above normal physiological levels. As such, it seems unlikely that these responses reflect the true physiological role of the trace amines. In this article previous studies showing responses to physiologically relevant concentrations of trace amines are reviewed, along with those showing a reciprocal relationship between trace amine levels and fluctuations in basal monoaminergic tone. On the basis of these studies it is hypothesized that the trace amines function as endogenous neuromodulators of classical monoamine neurotransmitters. These effects are seen as an altered neuronal sensitivity to monoamine neurotransmitters, with no change in neuronal excitability in the absence of neurotransmitter.

Amphetamines↗
PubMed1968

Restoration of the chronotropic effect of tyramine on rat atria after reserpine.

1. The restoration by various sympathomimetic amines of the chronotropic response to tyramine was studied on the isolated atria of rats pretreated with reserpine. The atria were exposed to the "restorative" sympathomimetic amine for 10 min, washed over a period of 1 hr and then tested with 10 muM tyramine. The effect of noradrenaline, dopamine and norphenylephrine before and after inhibition of monoamine oxidase by 0.5 mM iproniazid were compared with their alpha-methyl and N-alkyl analogues in their ability to restore the chronotropic response to tyramine.2. Noradrenaline and adrenaline restored the chronotropic response to tyramine, the degree of restoration depending on the concentration of the restorative amine used. Noradrenaline after iproniazid and alpha-methylnoradrenaline were equipotent and were about 1,000 times more active than noradrenaline where monoamine oxidase was not inhibited. Dopamine, epinine, norphenylephrine, phenylephrine, octopamine, synephrine and isoprenaline in the absence of monoamine oxidase inhibition had no effect. Dopamine after iproniazid and alpha-methyldopamine were equipotent and were about 1/10 as active as alpha-methylnoradrenaline. Norphenylephrine after iproniazid and metaraminol were equipotent and were about 1/500 as active as alpha-methylnoradrenaline. Octopamine after iproniazid was even less active. The N-methylated analogues were about 1/10 as active as their nor-compounds but the N-isopropyl analogue, isoprenaline, was devoid of activity.3. Dopamine after iproniazid and alpha-methyldopamine were inactive if a dopamine-beta-hydroxylase inhibitor, disulphiram or sodium diethyldithiocarbamate, was present.4. It is concluded that, in atria of reserpinized rats, (a) protection from monoamine oxidase increases; (b) N-substitution decreases; and (c) hydroxyl groups at the beta-carbon and ring positions 3 and 4 increase the capabilities of a sympathomimetic amine to restore the chronotropic response to tyramine.

Animals↗
PubMed1976

Brain concentrations of biogenic amine metabolites in acutely treated and ethanol-dependent rats.

1 Mass fragmentography was used to measure whole brain concentrations of some of the major metabolites of tyramine, octopamine, dopamine and noradrenaline in acutely treated and in ethanol-dependent rats. 2 Treatments with ethanol, either acutely or chronically, failed to alter significantly brain concentration of p-hydroxphenylacetic and p-hydroxymandelic acid (metabolites derived from tyramine and octopamine respectively). The effect on catecholamine metabolites was marked and therefore suggests that ethanol is selective in its effect on central metabolism of biogenic amines. 3 Acute ethanol treatment significantly increased brain concentration of homovanillic acid (HVA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Vanilmandelic acid (VMA) was not affected. All four metabolites (HVA, DOPAC, MHPG and VMA) were increased in the brains of rats rendered dependent on ethanol while still intoxicated (blood ethanol levels above 200 mg/dl). In ethanol-dependent rats undergoing ethanol withdrawal syndrome (no ethanol present in blood), the brain concentrations of HVA and DOPAC were normal while those of MHPG and VMA continued to be elevated. 4 From the decline in the concentrations of HVA and DOPAC after 50 mg pargyline/kg in control rats and rats acutely treated with ethanol, it was concluded that ethanol has no effect on the transport of phenolic acids across the blood brain barrier. 5 No reversal in the metabolism of catecholamines from an oxidative to a reductive pathway, analogous to that produced by ethanol in the periphery, could be established in the brain. 6 The increase in catecholamine metabolite concentrations after ethanol treatment, either acute or chronic, were interpreted as manifestations of increases catecholamine turnover.

Animals↗
PubMed1981

Tyramine antagonistic properties of AGN 1135, an irreversible inhibitor of monoamine oxidase type B.

1 The effects of the irreversible monoamine oxidase (MAO) inhibitors, AGN 1133, AGN 1135 and (-)-deprenyl, on tyramine and noradrenaline responses and uptake of [3H]-metaraminol were investigated in the isolated vas deferens of the rat. Uptake of [3H]-metaraminol and [3H]-octopamine was compared in mouse vas deferens. The modification of tyramine and noradrenaline-induced pressor responses by AGN 1133 and AGN 1135 was examined in anaesthetized rats and cats. 2 AGN 1133 (7.5 x 10(-6)M) greatly potentiated responses to tyramine in the rat isolated vas deferens. Both AGN 1135 and (-)-deprenyl inhibited tyramine responses selectively at concentrations above 10(-5)M (which caused almost complete inhibition of MAO types A and B) but tyramine responses were potentiated on washing out the inhibitors. 3 AGN 1135 (10(-4)M) and (-)-deprenyl (10-5)M) inhibited [3H]-metaraminol uptake by about 20% in rat and mouse vas deferens; neither inhibitor affected [3H]-octopamine uptake in mouse vas deferens. Desmethylimipramine (10(-6)M) inhibited amine uptake by more than 70%. 4 AGN 1133 (1.5 mg/kg) potentiated pressor responses to tyramine in rats and cats whereas AGN 1135 (1.5 mg/kg) did not. 5 AGN 1135 possesses tyramine antagonistic activity which is qualitatively similar to that of (-)-deprenyl but which cannot satisfactorily be explained by inhibition of neuronal or granula amine uptake.

Animals↗
PubMed1978

On the disulfiram-like effect of coprine, the pharmacologically active principle of Coprinus atramentarius.

Coprine or disulfiram was given to rats in various doses at various time intervals before the administration of 2 g/kg ethanol. The ratio acetaldehyde/ethanol in the alveolar air was measured by gas chromatography and was taken as an index of the aldehyde dehydrogenase (ALDH) activity. The activity of dopamine beta-hydroxylase (DBH) was estimated in the same animals by measuring the amount of 14C-octopamine formed from 14C-tyramine in the heart. Coprine and disulfiram both caused an increase in the acetylaldehyde/ethanol ratio, coprine being more potent than disulfiram. Disulfiram, but not coprine, reduced the net yield of 14C-octopamine. In rats pretreated with either coprine or disulfiram, blood-pressure and heart-rate were recorded before and after intraperitoneal injections of 0.4 g/kg ethanol. In both cases ethanol caused a marked and rapid fall in blood-pressure. However, this effect was accompanied by tachycardia only in animals treated with coprine. It is concluded that coprine like disulfiram inhibits ALDH, but only disulfiram causes an additional inhibition of DBH. This difference may account for differences in the cardiovascular response to ethanol.

Agaricales↗
PubMed1986

Peptidergic modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre.

The effects of a range of neuropeptides were investigated on the membrane potential of the Schwann cells of the giant nerve fibre of the tropical squid. Vasoactive intestinal peptide (VIP) produced a dose-dependent, long-lasting hyperpolarization of the Schwann-cell membrane potential. Among peptides structurally related to VIP, similar effects were produced by peptide histidine isoleucine (PHI) but not by secretin and glucagon. Substance P and somatostatin also hyperpolarized the Schwann-cell membrane potential but via receptor systems distinct from those activated by VIP. Methionine enkephalin ([Met]-enkephalin) blocked the actions of all the above peptides as well as the effects of DL-octopamine and carbachol. The actions of [Met]-enkephalin upon the VIP responses were antagonized by naloxone. VIP produces its effects on the Schwann-cell membrane potential via a receptor system that is independent from those described previously which mediate the effects of carbachol and DL-octopamine. However, VIP can potentiate the effects of the latter systems. The actions of VIP on the Schwann cell are unlikely to be mediated via changes in adenosine 3',5'-cyclic monophosphate (cyclic AMP) levels and are insensitive to changes in the level of extracellular calcium in the superfusate. The actions of VIP are, however, potentiated in the presence of low concentrations of lithium ions suggesting that the VIP receptor may mediate its effects by inducing the hydrolysis of polyphosphatidylinositols in the Schwann-cell membrane. Evidence is presented for the existence of an endogenous VIP-like component in the normal hyperpolarizing action of giant-axon activity on the membrane potential of the Schwann cell.

Animals↗
PubMed1977

Can hepatic coma be caused by a reduction of brain noradrenaline or dopamine?

Intraventricular infusions of octopamine which raised brain octopamine concentrations more than 20 000-fold resulted in reductions in brain noradrenaline and dopamine by as much as 90% without affecting the alertness or activity of normal rats. As this reduction of brain catecholamines is much greater than any reported in hepatic coma, we do not believe that values observed in experimental hepatic failure have aetiological significance for the encephalopathy that ensues.

Animals↗
PubMed1994

Ca2+ signaling in Sf9 insect cells and the functional expression of a rat brain M5 muscarinic receptor.

The purpose of the present study was to examine Ca2+ signaling mechanisms in Sf9 cells and to demonstrate expression and functional linkage of a mammalian receptor to changes in cytosolic free Ca2+ concentration ([Ca2+]i). Addition of p-octopamine (50 microM to fura 2-loaded Sf9 cells produced a small transient increase in [Ca2+]i from a basal level of 58 +/- 10 to 194 +/- 7.6 (SD) nM. The response to octopamine was inhibited by both cyproheptadine and chlorpromazine and was mimicked by clonidine. In contrast, [Ca2+]i did not change in response to dopamine (50 microM), substance P (50 nM), histamine (50 microM), ATP (50 microM), acetylcholine (10 or 100 microM), carbachol (10 or 100 microM), serotonin (50 microM), epinephrine (10 microM), or bradykinin (50 nM). The Ca(2+)-adenosinetriphosphatase inhibitors thapsigargin (200 nM) and 2,5-di-tert-butylhydroquinone (BHQ; 10 microM) increased [Ca2+]i to 307 +/- 13 and 137 +/- 20 nM, respectively. In contrast to BHQ, the response to thapsigargin was attenuated by La3+ or removal of extracellular Ca2+ and increased by elevation of extracellular Ca2+. These results suggest that thapsigargin but not BHQ stimulates Ca2+ influx. The rat brain muscarinic receptor (subtype M5) was incorporated into the baculovirus by homologous recombination. Addition of carbachol (100 microM) increased [Ca2+]i from 92.7 +/- 6.4 to 480 +/- 26 nM in Sf9 cells infected with recombinant virus containing the M5 receptor cDNA. The effect of carbachol on [Ca2+]i was concentration dependent with a 50% effective concentration of approximately 30 microM and was blocked by atropine (10 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗