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PubMed1980

Action of formamidine pesticides on octopamine receptors.

The formamidines are a structurally novel group of pesticides of growing importance in the control of mites, cattle ticks and certain orders of insects which have become resistant to conventional acaricides and insecticides. Their mode of action is complex with dose-dependent lethal and subletahal effects. At sublethal levels they cause behavioural changes in the target pest species (for example in feeding and in mating behaviours), changes which are responsible for the protective effects on crops and livestock. Although many suggestions have been made for the underlying biochemical mechanism, including inhibition of monoamine oxidase activity, uncoupling of respiration and blockade of neuromuscular transmission, no direct evidence has been presented. Another possibility is interaction with octopamine receptors in the central nervous system. We report here that the formamidine acaricide/insecticide, chlordimeform (CDM), and its demethylated deivative can mimic the actions of octopamine at the locust neuromuscular junctions. This gives the clearest evidence to date of the site of action of the formamidines and indicates a novel mode of action for these pesticides.

Amidines↗
PubMed2003

Functionally distinct dopamine and octopamine transporters in the CNS of the cabbage looper moth.

A cDNA was cloned from the cabbage looper Trichoplusia ni based on similarity to other cloned dopamine transporters (DATs). The total nucleotide sequence is 3.8 kb in length and contains an open reading frame for a protein of 612 amino acids. The predicted moth DAT protein (TrnDAT) has greatest amino acid sequence identity with Drosophila melanogasterDAT (73%) and Caenorhabditis elegansDAT (51%). TrnDAT shares only 45% amino acid sequence identity with an octopamine transporter (TrnOAT) cloned recently from this moth. The functional properties of TrnDAT and TrnOAT were compared through transient heterologous expression in Sf9 cells. Both transporters have similar transport affinities for DA (Km 2.43 and 2.16 micro m, respectively). However, the competitive substrates octopamine and tyramine are more potent blockers of [3H]dopamine (DA) uptake by TrnOAT than by TrnDAT. D-Amphetamine is a strong inhibitor and l-norepinephrine a weak inhibitor of both transporters. TrnDAT-mediated DA uptake is approximately 100-fold more sensitive to selective blockers of vertebrate transporters of dopamine and norepinephrine, such as nisoxetine, nomifensine and dibenzazepine antidepressants, than TrnOAT-mediated DA uptake. TrnOAT is 10-fold less sensitive to cocaine than TrnDAT. None of the 15 monoamine uptake blockers tested was TrnOAT-selective. In situ hybridization shows that TrnDAT and TrnOAT transcripts are expressed by different sets of neurons in caterpillar brain and ventral nerve cord. These results show that the caterpillar CNS contains both a phenolamine transporter and a catecholamine transporter whereas in the three invertebrates whose genomes have been completely sequenced only a dopamine-selective transporter is found.

Amino Acid Sequence↗
PubMed2000

Interaction of Na+, K+, and Cl- with the binding of amphetamine, octopamine, and tyramine to the human dopamine transporter.

Little information is available on the role of Na+, K+, and Cl- in the initial event of uptake of substrates by the dopamine transporter, i.e., the recognition step. In this study, substrate recognition was studied via the inhibition of binding of [3H]WIN 35,428 [2beta-carbomethoxy-3beta-(4-fluorophenyl)[3H]tropane], a cocaine analogue, to the human dopamine transporter in human embryonic kidney 293 cells. D-Amphetamine was the most potent inhibitor, followed by p-tyramine and, finally, dl-octopamine; respective affinities at 150 mM Na+ and 140 mM Cl- were 5.5, 26, and 220 microM. For each substrate, the decrease in the affinity with increasing [K+] could be fitted to a competitive model involving the same inhibitory cation site (site 1) overlapping with the substrate domain as reported by us previously for dopamine. K+ binds to this site with an apparent affinity, averaged across substrates, of 9, 24, 66, 99, and 134 mM at 2, 10, 60, 150, and 300 mM Na+, respectively. In general, increasing [Na+] attenuated the inhibitory effect of K+ in a manner that deviated from linearity, which could be modeled by a distal site for Na+, linked to site 1 by negative allosterism. The presence of Cl- did not affect the binding of K+ to site 1. Models assuming low binding of substrate in the absence of Na+ did not provide fits as good as models in which substrate binds in the absence of Na+ with appreciable affinity. The binding of dl-octopamine and p-tyramine was strongly inhibited by Na+, and stimulated by Cl- only at high [Na+] (300 mM), consonant with a stimulatory action of Cl- occurring through Na+ disinhibition.

Adrenergic Uptake Inhibitors↗
PubMed2000

Activation of a heterologously expressed octopamine receptor coupled only to adenylyl cyclase produces all the features of presynaptic facilitation in aplysia sensory neurons.

Short-term behavioral sensitization of the gill-withdrawal reflex after tail stimuli in Aplysia leads to an enhancement of the connections between sensory and motor neurons of this reflex. Both behavioral sensitization and enhancement of the connection between sensory and motor neurons are importantly mediated by serotonin. Serotonin activates two types of receptors in the sensory neurons, one of which is coupled to the cAMP/protein kinase A (PKA) pathway and the other to the inositol triphosphate/protein kinase C (PKC) pathway. Here we describe a genetic approach to assessing the isolated contribution of the PKA pathway to short-term facilitation. We have cloned from Aplysia an octopamine receptor gene, Ap oa(1), that couples selectively to the cAMP/PKA pathway. We have ectopically expressed this receptor in Aplysia sensory neurons of the pleural ganglia, where it is not normally expressed. Activation of this receptor by octopamine stimulates all four presynaptic events involved in short-term synaptic facilitation that are normally produced by serotonin: (i) membrane depolarization; (ii) increased membrane excitability; (iii) increased spike duration; and (iv) presynaptic facilitation. These results indicate that the cAMP/PKA pathway alone is sufficient to produce all the features of presynaptic facilitation.

Action Potentials↗
PubMed1964

I-OCTOPAMINE IN CITRUS: ISOLATION AND IDENTIFICATION.

l-Octopamine, [l-p-hydroxy-alpha-(aminomethyl)benzyl alcohol], has been isolated and identified from extracts of juice and leaves of the Meyer lemon. Identification was by chromatography, optical rotation, ultraviolet absorption curves, fluorescence spectra, and infrared spectroscopy. l-Octopamine has not previously been isolated and identified from plants.

Chromatography↗
PubMed1974

Octopamine: presence in single neurons of Aplysia suggests neurotransmitter function.

Octopamine has been identified and measured in individual neurons from Aplysia californica. Neither dopamine nor norepinephrine was detected in these cells. Thus, in Aplysia there may be separate populations of catecholaminergic and monophenolaminergic cells. Octopamine may have functions of its own in the central nervous system of mollusks.

Animals↗
PubMed1988

Gastric mill activity in the lobster. II. Proctolin and octopamine initiate and modulate chewing.

1. The neuromodulators proctolin and octopamine were injected into the circulatory system of lobsters, and the subsequent reaction of their gastric mill was analyzed with the help of an endoscope. 2. Injections of proctolin into the dorsal heart sinus elicited chewing with period durations of 5-60 s after a latency of 53 +/- 42 s (n = 32 injections). The threshold dose was 1 ml of 1.5 X 10(-7) M, which results in an estimated concentration of 3 X 10(-9) M in the blood. 3. The effects of proctolin on the coordination of the three teeth of the gastric mill is dose dependent. Proctolin injections of 1 ml of 1.5 X 10(-6) M elicited chewing in the squeeze mode, 1 ml of 1.5 X 10(-4) M triggered chewing in the cut-and-grind mode. Both modes are different in terms of coordination and usage of functionally different parts of the teeth. 4. An increase in the proctolin dose causes an increase of the duty cycle (ratio of closing duration to period duration) of the chewing from 0.19 to 0.51. The corresponding period duration shortens (from 30.8 to 9.9 s) at intermediate doses, but lengthens to 16.6 s at high doses because the closing duration goes up. 5. Chewing following a single injection can last between 2 and 30 min. Besides more or less stereotypic chewing in one of the basic modes, variations occurred, such as chewing of just the lateral teeth, cycle-by-cycle switching between different modes, or double bites of either the lateral teeth or the medial tooth. 6. Proctolin increased the strength of reflex bites, which could be elicited by mechanical stimulation of the cardiac sac. 7. Octopamine elicited not only irregular chewing, but also other reactions such as struggling, only if high doses, between 1 ml of 1.5 X 10(-4) and 1.5 X 10(-3) M were given, which correspond to an estimated concentration in the blood of between 3 X 10(-6) and 3 X 10(-5) M. 8. The proctolin effects on the gastric mill match the spontaneously occurring behavioral repertoire of the gastric mill, and they are explainable with known properties of the gastric central pattern generator and its sensitivity to proctolin.

Animals↗
PubMed2001

Mixtures of octopamine and serotonin have nonadditive effects on the CNS of the medicinal leech.

It is well established that neural networks respond to a wide variety of modulatory substances by which they can become reconfigured, yet few studies have examined the effects of neurotransmitter mixtures on such networks. In a previous study of the medicinal leech using triple intracellular recordings, we found that stimulation of identified mechanosensory neurons activated both the serotonergic cell 21 (a swimgating neuron) and the dorsal lateral octopamine (DLO) cell. Because these findings suggested that serotonin (5-HT) and octopamine (OA) may be released together, we investigated the effects of 5-HT and OA mixtures on isolated nerve cords of Hirudo medicinalis (which contained both head and tail brains). Fifty micromolar OA, 50 microM 5-HT, or a mixture of 50 microM OA and 50 microM 5-HT was bath applied to the nerve cord under constant perfusion conditions. Additional experiments were performed with combinations of either 25 or 100 microM OA and 5-HT. Neural activity was examined specifically in the segmentally repeated dorsal posterior (DP) nerve because it has been shown to contain identified swim motor units. Nonadditive effects of amine combinations were most apparent in their ability to decrease overall activity in the DP nerve and to alter patterned motor activity in the form of fictive swimming. Whereas swim burst activity has been previously shown to increase in nerve cords bathed in either 5-HT or OA solutions alone, we demonstrated that a mixture of the two amines resulted in a robust decrease in the number of swim bursts expressed and an inhibition of swim activity in preparations already swimming. Most compelling was the observation that when the amine mixture was replaced with normal saline, swim burst activity increased dramatically. We discuss that the effects of amine mixtures may be due to their interaction with descending interneurons known to trigger and inhibit swimming as the mixture-induced effects were not observed in nerve cords lacking the head and tail brains. Because the net effect of the two amines was not simply additive (i.e., 5-HT or OA is known to activate swimming, yet the mix inhibits swimming), this result reveals yet another layer of complexity inherent in "simpler" invertebrate nervous systems.

Animals↗
PubMed2001

Activation and reconfiguration of fictive feeding by the octopamine-containing modulatory OC interneurons in the snail Lymnaea.

We describe the role of the octopamine-containing OC interneurons in the buccal feeding system of Lymnaea stagnalis. OC neurons are swallowing phase interneurons receiving inhibitory inputs in the N1 and N2 phases, and excitatory inputs in the N3 phase of fictive feeding. Although the OC neurons do not always fire during feeding, the feeding rate is significantly (P < 0.001) higher when both SO and OC fire in each cycle than when only the SO fires. In 28% of silent preparations, a single stimulation of an OC interneuron evokes the feeding pattern. Repetitive stimulation of the OC interneuron increases the proportion of responsive preparations to 41%. The OC interneuron not only changes both the feeding rate and reconfigures the pattern. Depolarization of the OC interneurons increases the feeding rate and removes the B3 motor neuron from the firing sequence. Hyperpolarization slows it down (increasing the duration of N1 and N3 phases) and recruits the B3 motor neuron. OC interneurons form synaptic connections onto buccal motor neurons and interneurons but not onto the cerebral (cerebral giant cell) modulatory neurons. OC interneurons are electrically coupled to all N3 phase (B4, B4Cl, B8) feeding motor neurons. They form symmetrical connections with the N3p interneurons having dual electrical (excitatory) and chemical (inhibitory) components. OC interneurons evoke biphasic synaptic inputs on the protraction phase interneurons (SO, N1L, N1M), with a short inhibition followed by a longer lasting depolarization. N2d interneurons are hyperpolarized, while N2v interneurons are slowly depolarized and often fire a burst after OC stimulation. Most motor neurons also receive synaptic responses from the OC interneurons. Although OC and N3p interneurons are both swallowing phase interneurons, their synaptic contacts onto follower neurons are usually different (e.g., the B3 motor neurons are inhibited by OC, but excited by N3p interneurons). Repetitive stimulation of OC interneuron facilitates the excitatory component of the biphasic responses evoked on the SO, N1L, and N1M interneurons, but neither the N2 nor the N3 phase interneurons display a similar longer-lasting excitatory effect. OC interneurons are inhibited by all the buccal feeding interneurons, but excited by the serotonergic modulatory CGC neurons. We conclude that OC interneurons are a new kind of swallowing phase interneurons. Their connections with the buccal feeding interneurons can account for their modulatory effects on the feeding rhythm. As they contain octopamine, this is the first example in Lymnaea that monoaminergic modulation and reconfiguration are provided by an intrinsic member of the buccal feeding network.

Action Potentials↗
PubMed1980

Effect of isomers of octopamine on in vitro reactivity of vascular smooth muscle of rats.

The vascular reactivity to DL-ortho-, meta-, and para-octopamine was tested in vitro in aortic smooth muscle of the rat. When reactivities were compared on a molar basis with L-phenylephrine, an alpha-adrenergic agonist, the potencies of the three isomers were: 0.7500, 0.0075 and 0.0038 times that of phenylephrine for the m-, p- and o-isomer, respectively, Thus, of the three isomers, DL-m-octopamine had the greatest alpha-adrenergic activity in vitro as it did in vivo in earlier studies. Additional studies showed L-phenylephrine to induce about one-third the vascular response induced by L-norepinephrine.

Animals↗
PubMed1977

Catecholamine and octopamine concentrations in brains of patients with Reye syndrome.

Dopamine, norepinephrine, and octopamine levels were estimated in regions of brains obtained postmortem from children who died with Reye syndrome and from age-matched controls. Hypothalamic norepinephrine levels were greatly decreased (to 30 percent of control, p less than 0.02) and octopamine levels were increased (to 700 percent of control, p less than 0.01). Levodopa had little effect on the physiologic condition of the patients. However, CNS dopamine and homovanillic concentrations were not elevated by levodopa, indicating that in the present cases levodopa was not metabolized to its catecholamine products. The findings indicate that the encephalopathy of Reye syndrome (as in other types of hepatic coma) may be linked to the presence of false transmitters in the brain and that levodopa is a rational therapy if administered before irreversible CNS changes occur.

Brain Chemistry↗
PubMed2006

Octopamine mediates thermal preconditioning of the locust ventilatory central pattern generator via a cAMP/protein kinase A signaling pathway.

We investigated the role of biogenic amines in generating thermoprotection of the ventilatory motor pattern circuitry in Locusta migratoria. Levels of octopamine (OA) and dopamine (DA) in the metathoracic ganglion decreased during heat stress. We measured the thermosensitivity of central pattern generation in response to a ramped increase of temperature in semi-intact preparations. OA, DA, and tyramine (TA) were either bath applied or injected into the locust hemocoel 4-8 h before testing. Neither TA nor DA modified the thermotolerance of ventilatory motor pattern generation. However, OA treatment by bath applications (10(-4) M OA) or by injections into the hemocoel (2 microg/10 microl OA) mimicked heat shock preconditioning and improved the thermotolerance of the motor pattern by increasing the failure temperature and by decreasing the time taken to recover operation after a return to room temperature. Heat shock-induced thermoprotection was eradicated in locusts preinjected with epinastine (Oct betaR antagonist). Neuropil injections of the cAMP agonist and protein kinase A (PKA) activator, Sp-cAMPs, both conferred thermoprotection in control locusts and rescued thermoprotection in epinastine-treated HS locusts. Similar injections of the PKA inhibitor Rp-cAMPs blocked the thermoprotective effect of bath-applied OA. Octopamine-mediated thermoprotection was also abolished with neuropil injections of cycloheximide or actinomycin D, indicating a requirement for transcription and translation. We conclude that OA has a crucial role in triggering protein synthesis-dependent physiological adaptations to protect CNS function during heat stress by activating a cAMP/PKA pathway.

Action Potentials↗
PubMed1991

Characterization and pharmacological studies of an octopamine-sensitive adenylate cyclase from nerve cord of Locusta migratoria.

An octopamine-sensitive adenylate cyclase that is insensitive to stimulation by dopamine (DA) and 5-hydroxytryptamine (5-HT), was studied in a homogenized nerve cord preparation of the migratory locust, Locusta migratoria. The enzyme complex is similar to catecholamine-sensitive cyclases from mammals with respect to pH-optimum, requirement for Mg++ and GTP, and sensitivity to forskolin. The octopamine-mediated elevation of adenylate cyclase activity is antagonized by a variety of drugs with the following order of potency: mianserin greater than phentolamine greater than promethazine greater than gramine greater than cyproheptadine greater than cis-flupenthixol greater than chlorpromazine greater than metoclopramide.

Adenylyl Cyclases↗
PubMed2003

Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila.

The catecholamines play a major role in the regulation of behavior. Here we investigate, in the fly Drosophila melanogaster, the role of dopamine and octopamine (the presumed arthropod homolog of norepinephrine) during the formation of appetitive and aversive olfactory memories. We find that for the formation of both types of memories, cAMP signaling is necessary and sufficient within the same subpopulation of mushroom-body intrinsic neurons. On the other hand, memory formation can be distinguished by the requirement for different catecholamines, dopamine for aversive and octopamine for appetitive conditioning. Our results suggest that in associative conditioning, different memories are formed of the same odor under different circumstances, and that they are linked to the respective motivational systems by their specific modulatory pathways.

Animals↗
PubMed1987

Octopamine- and cyclic AMP-stimulated phosphorylation of a protein in Limulus ventral and lateral eyes.

The biogenic amine octopamine (OCT) fulfills most of the criteria as a neurotransmitter of efferent fibers that project to lateral and ventral eyes of the horseshoe crab, Limulus polyphemus. OCT is synthesized by and released from the efferent fibers, and OCT mimics many of the effects of endogenous efferent activity. OCT stimulates an increase in intracellular adenosine 3',5'-monophosphate (cAMP) in both ventral and lateral eyes, and many of the physiological effects of OCT in these eyes appear to be mediated via cAMP-dependent mechanisms. Here we show that OCT, acting apparently through an OCT-specific receptor, stimulates the increased phosphorylation of a protein with an apparent molecular weight of 122 kDa in both ventral and lateral eyes. This protein is also phosphorylated in response to 8-bromo cAMP and forskolin, suggesting that its phosphorylation involves activation of a cAMP-dependent protein kinase. We present evidence that the 122 kDa protein may be widely distributed in the Limulus visual system but that its phosphorylation in intact tissue in response to OCT, or agents acting through cAMP, may be restricted to portions containing photoreceptor cell bodies. The 122 kDa protein is quantitatively a major cellular protein in the photoreceptor cell body enriched portions of the ventral eye, its isoelectric point is between pH 6.2 and 6.4, and it is associated with both cell membranes and the cytoplasm. The function of this protein is not yet known. It may be important in mediating one or more of the effects of octopamine on Limulus vision.

Animals↗
PubMed1983

The cardiorespiratory impairment in cirrhosis and sepsis. An experimental interpretation using octopamine infusion.

The effects of octopamine on systemic and pulmonary circulation and on respiratory parameters have been studied in ten O2 100% breathing pigs. A rise in cardiac index (CI) due to an increase in the dynamics of the left ventricle and a progressive hypoxemia, notwithstanding the hyperventilation, was found. The decrease in arterial O2 tension was due to a rise in the pulmonary shunt fraction (QS/QT). The statistical analysis of cardiorespiratory parameters demonstrated that the high flow state linked with a non-Starling mechanism was the causing factor of a ventilation: perfusion ratio (VA/QT) decrease, which led to the rise in QS/QT. Also, a decrease in the lung compliance simultaneous to the increased blood flow was observed. It is suggested that octopamine may play a role in the pathogenesis of the cardiorespiratory hemodynamic impairment of cirrhosis and sepsis where high levels of this false neurotransmitter were observed.

Animals↗
PubMed1983

Comparative estimation of octopamine in the aortic smooth muscle, plasma and red blood cells of spontaneously hypertensive and Wistar Koyoto control rats.

Octopamine is an alpha agonist, the levels of which vary with age and in pathophysiological conditions. The levels of octopamine were found to be higher in the aortic smooth muscle and red blood corpuscles, but lower in the plasma of spontaneously hypertensive rats (SHR) than in the Wistar Koyoto rats. The importance of these variations are discussed.

2-Hydroxyphenethylamine↗
PubMed1980

Hepatic encephalopathy EEG and octopamine.

In a group of 30 patients with and without hepatic encephalopathy octopamine values were determined and EEG recorded. The data reported show no relationship between octopamine values and presence or seriousness of hepatic encephalopathy but showed a clear correlation between hepatic encophalopathy and electroencephologram disturbance.

Adult↗