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Octopamine reverses the isolation-induced increase in trophallaxis in the carpenter ant Camponotus fellah.

Social deprivation is an unusual situation for ants that normally maintain continuous contact with their nestmates. When a worker was experimentally isolated for 5 days and then reunited with a nestmate, she engaged in prolonged trophallaxis. It is suggested that trophallaxis allows her to restore a social bond with her nestmates and to re-integrate into the colony, particularly via the exchange of colony-specific hydrocarbons. Octopamine reduced trophallaxis in these workers as well as hydrocarbon transfer between nestmates, but not hydrocarbon biosynthesis. Administration of serotonin to such 5-day-isolated ants had no effect on the percentage of trophallaxis. Administration of phentolamine alone, an octopamine antagonist, had no effect, but when co-administrated with octopamine it reduced the effect of octopamine alone and restored trophallaxis to control levels. Moreover, the observed effect of octopamine was not due to a non-specific effect on locomotor activity. Therefore, we hypothesise that octopamine mediates behaviour patterns linked to social bonding, such as trophallaxis. On the basis of an analogy with the role of norepinephrine in vertebrates, we suggest that the levels of octopamine in the brain of socially deprived ants may decrease, together with a concomitant increase in their urge to perform trophallaxis and to experience social contacts. Octopamine administration may reduce this social deprivation effect, and octopamine could therefore be regarded as being partly responsible for the social cohesion between nestmates in ant colonies.

Animal Communication↗

Tyramine and octopamine have opposite effects on the locomotion of Drosophila larvae.

Biogenic amines are believed to play important roles in producing behaviors. Although some biogenic amines have been extensively studied in both vertebrates and invertebrates, little is known about the effects of trace amines like tyramine and octopamine. We investigated how trace amines affect behaviors using quantitative morphometric methods on Drosophila Tbetah(nM18) and iav(N) mutants that have altered levels of tyramine and octopamine. Locomotion of wild-type and mutant third instar larvae was analyzed using Dynamic Image Analysis System (DIAS) software. We found that Tbetah(nM18) mutants, with elevated tyramine levels and reduced octopamine levels, had a severe locomotion phenotype. Mutant larvae spent much more time in pausing episodes than wild-type larvae and displayed a reduction in speed and linear translocation. The locomotion phenotype was partially rescued by feeding Tbetah(nM18) larvae octopamine, an effect that could be nullified with simultaneous feeding of tyramine. Feeding Tbetah(nM18) larvae yohimbine, an agent that inhibits the activity of Drosophila tyramine receptors, also improved some locomotion parameters. Feeding both octopamine and yohimbine further improved rescue efficiency. Simultaneously reducing the octopamine and tyramine levels as in iav(N) larvae, in contrast, led to a less severe behavioral phenotype than that of Tbetah(nM18) mutants. Feeding iav(N) larvae either tyramine or octopamine exerted only a minor improvement in locomotion. These results suggest that tyramine and octopamine have opposite effects on Drosophila larval locomotion regulation and that a balance between the two is important in producing normal behavior.

Animals↗

Octopamine-immunoreactive neurons in the central nervous system of the cricket, Gryllus bimaculatus.

The distribution of octopamine-immunoreactive neurons is described using whole-mount preparations of all central ganglia of the cricket, Gryllus bimaculatus. Up to 160 octopamine-immunoreactive somata were mapped per animal. Medial unpaired octopamine-immunoreactive neurons occur in all but the cerebral ganglia and show segment-specific differences in number. The position and form of these cells are in accordance with well-known, segmentally-organized clusters of large dorsal and ventral unpaired medial neurons demonstrated by other techniques. In addition, bilaterally arranged groups of immunoreactive somata have been labelled in the cerebral, suboesophageal and terminal ganglia. A detailed histological description of octopamine-immunoreactive elements in the prothoracic ganglion is given. Octopamine-immunoreactive somata and axons correspond to the different dorsal unpaired medial cell types identified by intracellular single-cell staining. In the prothoracic ganglion, all efferent neurons whose primary neurites are found in the fibre bundle of dorsal unpaired cells are immunoreactive. Intersegmental octopamine-immunoreactive neurons are also present. Collaterals originating from dorsal intersegmental fibres terminate in different neuropils and fibre tracts. Fine varicose fibres have been located in several fibre tracts, motor and sensory neuropils. Peripheral varicose octopamine-immunoreactive fibres found on several nerves are discussed in terms of possible neurohemal releasing sites for octopamine.

Animals↗

Release of octopamine by Leydig cells in the central nervous system of the leech Macrobdella decora, and its possible neurohormonal role.

1. The release of octopamine by the central nervous system of the leech Macrobdella decora was examined. Isolated ganglia or chains of ganglia were incubated in salines of varying composition, and the release of octopamine into the perfusate was measured using a radioenzymatic method. In some experiments this release was correlated with the electrical activity of the octopamine-containing Leydig cells, as measured via a microelectrode in the cell body. 2. Chains of ganglia incubated in normal saline released 0.04 pmol octopamine/ganglion/3 min incubation period. This amount was not significantly increased by either the monoamine oxidase inhibitor iproniazid phosphate (0.1 mM) or the uptake inhibitor desipramine (10 microM) alone, but was by both together. Nominally calcium-free saline containing 20 mM Mg++ significantly decreased octopamine release. 3. High K+ saline increased octopamine release significantly in both standard saline and one containing the blocking agents. This increase was sevenfold in saline containing iproniazid phosphate and desipramine, and was significantly greater than that obtained in saline without the blockers. This provides further evidence for the role of octopamine as a neuroactive substance in the leech by indicating the existence of possible mechanisms for its uptake and/or inactivation. 4. Octopamine release was positively correlated with the firing frequency of Leydig cells. No release was detectable when the cells were prevented from firing by the injection of hyperpolarizing current. Release was frequency-dependent when the cells fired at frequencies of 0.1-1.0 spikes/s. Elevating the external calcium concentration from 1.8 to 5.4 mM significantly increased octopamine release at all frequencies tested, except for 0 spikes/s, at which release remained below detectabilty.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effect of chlordimeform and clonidine on the turnover of P-octopamine in rat hypothalamus and striatum.

The effect of the invertebrate octopamine agonists chlordimeform and clonidine on the concentration and turnover of p-octopamine and m- and p-tyramine was determined in rat hypothalamus and striatum. Clonidine (0.25 mg/Kg, s.c.) did not alter the concentration of p-octopamine in the hypothalamus or p-tyramine in the striatum. Administration of chlordimeform (50 mg/Kg, i.p.) resulted in an increase in p- and m-tyramine concentrations in the striatum but not that of p-octopamine in the hypothalamus. This increase in the tyramine isomers is consistent with the ability of chlordimeform and its metabolite, demethylchlordimeform, to inhibit monoamine oxidase (MAO). The concurrent administration of chlordimeform (50 mg/Kg, i.p.) and pargyline (75 mg/Kg, i.p.) produced a significant decrease in the accumulation of octopamine in the hypothalamus but not in the striatum. In contrast, the concurrent administration of clonidine (0.25 mg/Kg, s.c.) and pargyline (75 mg/Kg, i.p.) caused a significant decrease in the accumulation of octopamine in the striatum but not hypothalamus. These results show that the turnover of octopamine in the hypothalamus and striatum is decreased by chlordimeform and clonidine, respectively. Further, clonidine is known to modulate the turnover of amines in mammalian noradrenergic nerve terminals by an action at presynaptic adrenergic receptors. These data suggest that two mechanisms, one involving presynaptic adrenergic receptors in the striatum, and the other involving as yet unidentified receptors in the hypothalamus, modulate the turnover of octopamine in the mammalian brain.

Amidines↗

Effects of drugs interfering with the metabolism of octopamine on blood pressure of rats.

1. p-Octopamine injected in lateral ventricle of conscious spontaneously hypertensive rats decreased systolic blood pressure (SBP). 2. Precursors of octopamine--tyrosine, tyramine and phenylethanolamine (PEA)--had the same effect. The administration of pargyline, a MAO inhibitor, which increased brain octopamine, resulted in a reduction of systolic blood pressure; and this decrease was greater after administration of octopamine precursors and PEA. 3. Similarly, drugs known to inhibit activity of phenylethanolamine N-methyl-transferase (PNMT) and to increase brain octopamine level such as SKF 64139 and DCMB decreased SBP. 4. p-Octopamine hypotension was not antagonized by piperoxan, yohimbine and prazosin, a relatively selective antagonist of post-synaptic alpha adrenoceptors. 5. These results suggest that octopamine may be involved in central blood pressure regulation, and the receptors sensitive to octopamine appeared to be distinct from those receptive to the catecholamines.

Animals↗

Stimulation of cyclic AMP formation and nerve electrical activity by octopamine in the terminal abdominal ganglion of the female gypsy moth Lymantria dispar.

The biogenic amine octopamine is known to be present in the abdominal ganglia of some insects, but the expression of functional octopamine receptors in these neuronal structures has not yet been characterized. In the present study, we describe the presence in the female gypsy moth terminal abdominal ganglion (TAG), a key structure in the control of the insect reproductive behavior, of an octopamine receptor coupled to stimulation of adenylyl cyclase through the GTP-binding protein G(s). The rank order of potency of different antagonists, which discriminate between the different classes of octopamine receptors, indicated the involvement of the neuronal type 3 receptor. The octopamine-stimulated adenylyl cyclase activity was inhibited by Ca(2+) in the low micromolar range and by activation of either protein kinase A or protein kinase C. In the isolated TAG, bath application of octopamine caused an increase of the spontaneous bursting activity of the emerging nerve of the 5th pair (V), whereas the antagonist mianserin reduced the nerve spiking activity and blocked the stimulatory effect of octopamine. These data demonstrate that the gypsy moth TAG expresses functional octopamine receptors, which may participate in the neuronal control of the insect reproductive behavior.

Abdomen↗

Octopamine inhibits synaptic transmission at the larval neuromuscular junction in Drosophila melanogaster.

The effect of octopamine, a biogenic amine, on synaptic transmission at the neuromuscular junction (NMJ) in first instar larvae of Drosophila melanogaster was examined using the patch clamp technique. Muscle cells were voltage-clamped at -60 mV in the whole-cell configuration, and nerve-evoked excitatory junctional currents (EJCs) and miniature excitatory junctional currents (MEJCs) were recorded. Octopamine significantly decreased the mean amplitude of nerve-evoked EJCs in a dose-dependent manner and increased the failure rate. However, the mean amplitude and amplitude distribution of MEJCs were not affected by octopamine. These results suggest that octopamine is acting presynaptically. This effect was abolished by pretreatment with the octopamine receptor blocker, yohimbine. On the other hand, octopamine significantly decreased the decay time constant of MEJCs from 6.0+/-0.3 ms (mean+/-S.E., n=16) to 4.2+/-0.3 ms (n=14) (p<0.001), which might be the effect on the kinetic properties of junctional glutamate receptor channels. However, the mean open time of extrajunctional glutamate receptor channels was not changed by octopamine. Taken together, these results suggest that octopamine inhibits synaptic transmission by affecting both pre- and postsynaptic mechanisms.

Animals↗

Octopamine.

Octopamine is highly concentrated in neurones of several invertebrate species. Unlike in mammals, octopaminergic neurones in invertebrates are spatially separated from catecholaminergic neurons. In identified nerve cells of Aplysia, however, this amine coexists with other putative neurotransmitters. Octopamine is synthesized in nerves from tyrosine and tyramine and metabolised mainly by monoamine oxidase. When lobster nerves are depolarized, octopamine is liberated by a Ca2+-dependent process. A specific adenylate cyclase is stimulated by octopamine in several invertebrates to activate phosphorylase in the cockroach, induce a light-flash in firefly lattern or inhibit rhythm contractions in locust muscle. All of these observations provide compelling evidence that octopamine is a neurotransmitter in invertebrates. In mammals octopamine is localised in nerves in peripheral tissues and brain where it seems to coexist with noradrenaline, the catecholamine being present in much higher concentrations. Octopamine is released from nerves together with noradrenaline and it may under certain conditions modify the actions of the adrenergic neurotransmitter. Octopamine is present in unusually high concentrations in certain neurological and hepatic diseases and may have a pathophysiological role.

Animals↗

Octopamine receptors in the honey bee and locust nervous system: pharmacological similarities between homologous receptors of distantly related species.

Honey bees are perhaps the most versatile models to study the cellular and pharmacological basis underlying behaviours ranging from learning and memory to sociobiology. For both aspects octopamine (OA) is known to play a vital role. The neuronal octopamine receptor of the honey bee shares pharmacological similarities with the neuronal octopamine receptor of the locust. Both, agonists and antagonists known to have high affinities for the locust neuronal octopamine receptor have also high affinities for the bee neuronal octopamine receptor. The distribution of receptors is more or less congruent between locusts and bees. Optic lobes and especially the mushroom bodies are areas of greatest octopamine receptor expression in both species, which mirrors the physiological significance of octopamine in the insect nervous system. The neuronal octopamine receptor of insects served as a model to study the pharmacological similarity of homologous receptors from distantly related species, because bees and locusts are separated by at least 330 million years of evolution.

Animals↗

Stimulatory effect of octopamine on beta 3-adrenoceptors to lower the uptake of [14C]-deoxy-D-glucose into rat adipocytes in vitro.

1. The effect of octopamine on beta 3-adrenoceptors has been studied in isolated adipocytes of Wistar rats using uptake of [14C]-deoxy-D-glucose as the indicator. 2. Octopamine (0.1-1 nmol 1-1) induced a concentration-dependent decrease of [14C]-deoxy-D-glucose uptake into the adipocytes and this inhibition was not influenced by haloperidol at concentrations sufficient to block dopaminergic receptors. 3. Pindolol and propranolol reversed this inhibition of octopamine in a concentration-dependent manner. The effect of octopamine was reduced in the presence of Rp-cyclic AMPS triethylamine, the membrane-permeable antagonist of cyclic AMP (cAMP), indicating the mediation of cAMP in this inhibition. 4. A direct effect of octopamine on beta 3-adrenoceptors was proved using the application of antibodies. In the presence of an antibody for beta 3-adrenoceptors, the actions of octopamine were concentration-dependently reduced in a manner similar to the decrease of BRL37344-induced inhibitions. 5. The same degree of diminished activities for octopamine as that of BRL37344, the well-known specific agonist of beta 3-adrenoceptors, was also obtained in isoprenline-desensitized adipocytes. Insulin-stimulated uptake of [14C]-deoxy-D-glucose into adipocytes was not modified by isoprenaline induced desensitization. 6. These results suggest that octopamine can activate beta 3-adrenoceptors to lower the glucose uptake through an increase of cAMP in rat white adipocytes.

Adipocytes↗

Differential blockade of octopamine and dopamine receptors by analogues of clozapine and metoclopramide.

1. Sulpiride, but not procainamide, antagonizes the excitatory effects of (+/-)-octopamine receptors in the Tapes ventricle. Neither compound attenuates dopamine excitation. 2. Clozapine will attenuate the effects of (+/-)-octopamine and (-)-alpha-methyl octopamine at the octopamine receptor but not the excitatory effect of dopamine at dopamine receptors. 3. Clozapine is more potent than its 2-positional isomer HF 2046 in attenuating octopamine excitation. However, HF 2046, unlike clozapine, will attenuate the excitatory effects of dopamine. 4. These data indicate that replacement of the 8-chloro substituent in the clozapine nucleus with a 2-chloro substituent decreases the ability of the compound to blockaed octopamine receptors. However, the 2-chloro-substituted compound (HF 2046) now has the added ability to blockade excitatory dopamine receptors. 5. The greater potency of clozapine than HF 2046 as an octopamine antagonist suggests that it is the 8-chloro-substituted aromatic ring of clozapine which overlaps the aromatic site usually occupied by the octopamine aromatic ring.

Animals↗

The role of neurohormonal octopamine during 'fight or flight' behaviour in the field cricket Gryllus bimaculatus.

Octopamine has been called the 'fight or flight' hormone of insects. We tested this hypothesis by measuring octopamine levels in the haemolymph of field crickets after fighting, flying, courting and escape behaviours. Octopamine levels in the cricket Gryllus bimaculatus increased during aggressive (agonistic) behaviour from baseline levels of 4.5 +/- 2.1 pg microliters-1 haemolymph to 24.3 +/- 15.2 pg microliters-1 haemolymph, regardless of whether the cricket won or lost the encounter. Octopamine levels also increased after 5 min of flying (to 44.6 +/- 22.3 pg microliters-1) and during courtship. However, crickets did not exhibit an increase in their haemolymph octopamine levels after performing an escape run. Therefore, neurohormonal octopamine shows some, but not all, of the characteristics that would be expected if it were a component of a nonspecific 'arousal' system. Rather, octopamine may be released as a neurohormone to prepare the animal for a period of extended activity or to assist the animal in recovering from a period of increased energy demand. Antennal contact with conspecifics may provide a sensory cue that results in the release of octopamine into the haemolymph.

Aggression↗

Pharmacologic analysis of positive chronotropic and inotropic responses to octopamine.

Effects of octopamine on sinus rate and atrial contractility were investigated using the isolated atrium preparation of the dog which perfused with heparinized arterial blood led from a support dog. When octopamine, dopamine or norepinephrine was administered into the cannulated sinus node artery, positive chronotropic and inotropic responses were dose-relatedly induced from 0.1 mug, 0.1 mug or 0.01 mug, respectively. The D.R.50 values (dose ratio at 50% maximum response) of octopamine, dopamine and norepinephrine are roughly 30-100: 30:1, respectively. The duration of action of octopamine was longest. Effects induced by octopamine were blocked by an adrenergic beta-blocking agent, alprenolol. Desmethyl-imipramine treatment significantly suppressed octopamine-induced effects but rather enhanced norepinephrine-induced ones. Octopamine-induced effects were not influenced by tetrodotoxin which blocked those induced by nicotine. From these results, it is concluded that positive chronotropic and inotropic responses to octopamine are mainly due to a tyramine-like action.

Alprenolol↗

Evaluation of isomers of octopamine for in vitro alpha-adrenergic stimulation of the aortic smooth muscle from spontaneously hypertensive rats.

Isomers of octopamine were tested for in vitro alpha-adrenergic stimulation of aortic smooth muscle of spontaneously hypertensive rats (SHR). In order to test the response of alpha 1-adrenoceptors to meta-, para-, and ortho-octopamine, alpha 2-adrenoceptors were blocked with 10(-7) M yohimbine, and to measure the response of alpha 2-adrenoceptors the alpha 1-adrenoceptors were blocked with 10(-7) M prazosin. The contractile response of aortic smooth muscle of SHR to stimulation by phenylephrine, m-, p-, and o-isomers of octopamine in the presence of yohimbine was not appreciably altered. However, administration of prazosin severely attenuated the response of muscles of these compounds indicating that like phenylephrine, the isomers of octopamine stimulate mainly alpha 1-adrenoceptors. The attenuation of contractile response to isomers of octopamine in the presence of prazosin was not as pronounced as in the case of phenylephrine. The comparative potencies of phenylephrine, m-, p-, and o-octopamine in the presence of 10(-7) M prazosin were 1:1.2:2.5:0.75, respectively. Thus, it appears that the isomers of octopamine, especially para- and meta-octopamine, play a much more important role in the physiology of vascular smooth muscle than has been thus far perceived.

Animals↗

Effects of octopamine on renal function in anaesthetized dogs.

Increased levels of octopamine in adrenergic nerve terminals and plasma have been implicated in the circulatory and renal disturbances of chronic hepatic failure. Little is known about its renal actions in normal animals. In the present study, DL-octopamine was administered both i.v. and into one renal artery of anaesthetized dogs in doses ranging between 25-200 micrograms/min (1.6-20 micrograms/kg/min). Octopamine was hypertensive in doses of 100 micrograms/min and more and this change was associated with a significant decrement in GFR and renal perfusion. This amine also exerted a direct tubular effect since decreased excretion of sodium and water occurred in the absence of blood pressure or renal perfusional changes when given i.v. When given into one renal artery octopamine produced only an ipsilateral antidiuresis and antinatriuresis, in the absence of any change to GFR or renal perfusion. Lithium clearances suggest that octopamine acts beyond the proximal tubule in altering the tubular reabsorption of salt and water. Because octopamine was found to increase blood pressure in the presence of a hypertensive infusion of noradrenaline, it is likely that this amine exerts a primary pharmacological effect rather than liberating noradrenaline from nerve terminals. Saline expansion (7% body weight), acute biliary obstruction, chronic cirrhosis with ascites, and chronic thoracic caval constriction with the production of ascites all abolish the effect of octopamine when administered at 100 micrograms/min. Though octopamine may directly influence renal perfusion, its possible role in liver disease remains uncertain.

Animals↗

Efferent neurotransmission of circadian rhythms in Limulus lateral eye. I. Octopamine-induced increases in retinal sensitivity.

Octopamine increases the sensitivity of the Limulus lateral eye in situ when injected beneath the cornea during the day. The effect of octopamine is dose-dependent with a threshold concentration of about 0.1 microM injected at 1 microliter/min for 15 min. Injection of 40 microM octopamine increases lateral eye sensitivity to approximately 70% of the nighttime level normally caused by the efferent output of a circadian clock. Injections of octopamine analogues and other candidate neurotransmitters indicate that the postsynaptic receptor mediating the increase of retinal sensitivity is relatively specific for the structure of octopamine. The postsynaptic receptor is tentatively classified as a type 2B octopamine receptor (Evans, P. D. (1981) J. Physiol. (Lond.) 318: 99-122). Clozapine suppresses the effects of both exogenous octopamine and the endogenous efferent neurotransmitter. Together with the results from Barlow et al. (Barlow, R. B., Jr., S. J. Bolanowski, Jr., and M. L. Brachman (1977) Science 197: 86-89) and Battelle et al. (Batelle, B. -A., J. A. Evans, and S. C. Chamberlain (1982) Science 216: 1250-1252) our study leads to the following conclusion: retinal efferents, driven by a circadian clock in Limulus brain, release octopamine that increases visual sensitivity.

Animals↗

Insect octopamine receptors: a new classification scheme based on studies of cloned Drosophila G-protein coupled receptors.

Insect octopamine receptors are G-protein coupled receptors. They can be coupled to second messenger pathways to mediate either increases or decreases in intracellular cyclic AMP levels or the generation of intracellular calcium signals. Insect octopamine receptors were originally classified on the basis of second messenger changes induced in a variety of intact tissue preparations. Such a classification system is problematic if more than one receptor subtype is present in the same tissue preparation. Recent progress on the cloning and characterization in heterologous cell systems of octopamine receptors from Drosophila and other insects is reviewed. A new classification system for insect octopamine receptors into "alpha-adrenergic-like octopamine receptors (OctalphaRs)", "beta-adrenergic-like octopamine receptors (OctbetaRs)" and "octopamine/tyramine (or tyraminergic) receptors" is proposed based on their similarities in structure and in signalling properties with vertebrate adrenergic receptors. In future studies on the molecular basis of octopamine signalling in individual tissues it will be essential to identify the relative expression levels of the different classes of octopamine receptor present. In addition, it will be essential to identify if co-expression of such receptors in the same cells results in the formation of oligomeric receptors with specific emergent pharmacological and signalling properties.

Animals↗