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Octopamine- and dopamine-sensitive adenylate cyclase in the brain of Locusta migratoria during its development.

Octopamine- and dopamine-sensitive adenylate cyclases were studied in the brain of Locusta migratoria during its metamorphosis. In the adult brain the effects of octopamine and dopamine on adenylate cyclase were additive, suggesting the presence of separate populations of adenylate cyclase-linked receptors for octopamine and dopamine. There are no separate receptors for noradrenaline. Octopamine stimulates adenylate cyclase in both adult and larval brain; however, in adult brain octopamine is more potent than in larval brain. Dopamine stimulates adenylate cyclase activity only in adult brain. The sensitivity of adenylate cyclase to octopamine changes during the development of the animal. Phentolamine and cyproheptadine are potent antagonists of octopamine-stimulated adenylate cyclase, while propranolol has a weak effect. No cytosol factor which would modulate either basal or octopamine-stimulated adenylate cyclase was found. The effect of GTP and octopamine on adenylate cyclase was synergistic in adult brain but not in larval brain, while the effect of GppNHp and octopamine was synergistic in both adult and larval brains.

Adenylyl Cyclases↗

Octopamine modulates photoreceptor function in the Limulus lateral eye.

Activity at night in efferent nerve fibers from a central circadian clock produces changes in photoreceptor function in the lateral compound eye of Limulus: the response to light is increased; membrane potential fluctuations (bumps) occurring in the dark are suppressed; and the duration of bumps occurring both in the dark and under dim illumination is increased (Barlow et al., 1977; Kaplan & Barlow, 1980; Barlow, 1983; Barlow et al., 1985). Efferent nerve terminals release octopamine when activated (Battelle et al., 1982; Battelle & Evans, 1984, 1986); exogenous octopamine in vitro produces some of the changes resulting from efferent nerve activity in vivo (Kass et al., 1988). We report here that the increase in both on-transient and steady-state response to light induced by octopamine in the lateral eye in vitro are concentration dependent with threshold at or below 100 nM, saturation at or above 100 microM, and half-maximal increase in the range 1-10 microM. Octopamine also reduces bump activity in the dark in a concentration-dependent way. Unlike the increase in light response, the dependence of this effect on octopamine concentration is extremely variable from specimen to specimen. The effects of exogenous octopamine on light response and bump activity can sometimes be reversed by removing octopamine from the medium bathing the in vitro preparation. Octopamine also increases bump duration, apparently in a concentration-dependent manner. We have not succeeded in reversing this increase in bump duration. The concentration dependence of changes in photoreceptor response described here agrees qualitatively with the dependence of cAMP levels on octopamine in Limulus photoreceptors (Kaupp et al., 1982), lending further support to the idea that cAMP acts as a second messenger in the circadian control of photoreceptor function. Our results also suggest that the changes induced in the transient and steady-state response to light by both efferent nerve activity and exogenous octopamine have a common origin, which may differ from that responsible for the modulation of bump activity.

Animals↗

Molecular and functional characterization of an octopamine receptor from honeybee (Apis mellifera) brain.

Biogenic amines and their receptors regulate and modulate many physiological and behavioural processes in animals. In vertebrates, octopamine is only found in trace amounts and its function as a true neurotransmitter is unclear. In protostomes, however, octopamine can act as neurotransmitter, neuromodulator and neurohormone. In the honeybee, octopamine acts as a neuromodulator and is involved in learning and memory formation. The identification of potential octopamine receptors is decisive for an understanding of the cellular pathways involved in mediating the effects of octopamine. Here we report the cloning and functional characterization of the first octopamine receptor from the honeybee, Apis mellifera. The gene was isolated from a brain-specific cDNA library. It encodes a protein most closely related to octopamine receptors from Drosophila melanogaster and Lymnea stagnalis. Signalling properties of the cloned receptor were studied in transiently transfected human embryonic kidney (HEK) 293 cells. Nanomolar to micromolar concentrations of octopamine induced oscillatory increases in the intracellular Ca2+ concentration. In contrast to octopamine, tyramine only elicited Ca2+ responses at micromolar concentrations. The gene is abundantly expressed in many somata of the honeybee brain, suggesting that this octopamine receptor is involved in the processing of sensory inputs, antennal motor outputs and higher-order brain functions.

Amino Acid Sequence↗

Comparison of the actions of octopamine and catecholamines on single neurones of the rat cerebral cortex.

1. The technique of microelectrophoresis was used to compare the actions of octopamine, noradrenaline and dopamine on single cortical neurones of the rat. 2. Octopamine both excited and depressed neurones of the cortex. Frequently cells depressed by noradrenaline were excited by octopamine; occasionally the converse was true. The time courses of action of the two amines also differed. Dopamine-elicited excitations were observed, but also were not correlated with octopamine-elicited effects. 3. When octopamine and noradrenaline both caused depressant effects, octopamine frequently was of less apparent potency than noradrenaline. When these amines were excitatory, octopamine appeared at least as and sometimes more potent than noradrenaline. 4. Octopamine was only weakly effective on cortical neurones identified by antidromic stimulation of the pyramidal tract, or synaptically excited by stimulation of the ventrobasal thalamus. 5. alpha-Flupenthixol and propranolol were without effect on octopamine-elicited changes in firing rate at doses which were effective in blocking the actions of dopamine and noradrenaline respectively. Metoclopramide did not block the actions of any of the three agonists, but had strong effects of its own. 6. The results suggest that receptors sensitive to octopamine, and which appear to be pharmacologically distinct from those previously categorized as noradrenaline and dopamine receptors, may exist on central neurones of the rat.

Animals↗

Modulation of spontaneous and reflex activity of crayfish leg motor neurons by octopamine and serotonin.

1. We compared the effects of octopamine and serotonin on the activity of crayfish leg motor neurons in an isolated preparation of the 4th thoracic ganglion. Spontaneous activity of leg promotor (swing phase in a forward walking crayfish) and remotor (stance phase) motor neurons consisted either of continuous promotor activity (with the remotor nerve silent) or alternating bursts of promotor and remotor activity. Octopamine and serotonin, at high concentrations (< or = 100 and < or = 20 microM, respectively), abolished spontaneous promotor activity and rhythmic bursting (if ongoing). Both amines induced tonic remotor nerve activity, but each amine activated different identified remotor motor neurons. 2. Reflex responses of remotor motor neurons to stimulation of thoracocoxal (TC) joint proprioceptors were modulated by octopamine and serotonin in characteristic ways. The muscle receptor (TCMRO) that signals joint remotion excited a subset of remotor motor neurons in an assistance reflex. The chordotonal organ (TCCO) that signals joint promotion excited different remotor motor neurons in a resistance reflex. Octopamine abolished assistance reflexes and facilitated resistance reflexes. One assistance group unit was inhibited, whereas reflex reversal was induced in another: this unit was now excited in a resistance reflex, rather than in an assistance reflex. The responses of resistance group remotor units were enhanced. Serotonin had the opposite effect on assistance group remotors: one unit was excited and generated a stronger assistance reflex. The effect of serotonin on resistance group remotor units was similar (but quantitatively different) to that of octopamine. 3. Both octopamine and serotonin modulated spontaneous motor output at concentrations below those required to inhibit promotor nerve activity. Rhythmic promotor and remotor bursting was abolished, and replaced with continuous promotor activity, by serotonin at 1 microM and octopamine at 1-10 microM. In nonbursting preparations, promotor activity could be excited (instead of inhibited) by either amine at lower concentrations. 4. Octopaminergic inhibition of spontaneous promotor activity was antagonized by mianserin (10 microM). Phentolamine at the same concentration was less effective as an antagonist. Serotonergic inhibition of promotor activity was not blocked by mianserin. Mianserin also antagonized inhibitory, but not excitatory, effects of octopamine on remotor reflex responses. Serotonergic modulation of these reflexes was not affected. 5. An intersegmental difference was found in aminergic inhibition of promotor nerve activity. Whereas the effect (at the higher concentrations used) was inhibition of promotor activity from T4, simultaneous recordings from promotor nerves of the more rostral ganglia T3 and T2 showed either promotor excitation, or inhibition that was significantly weaker than in T4. This may relate to the known postural effects of these amines in intact crayfish and lobsters. 6. We conclude that octopamine and serotonin are modulators of segmental reflexes in the crayfish walking system. Each amine "assembles" a unique remotor nerve reflex response from different combinations of remotor units. In the case of octopamine, inhibitory effects are mediated by a mianserin-sensitive receptor, whereas excitatory effects are mediated by a mianserin-insensitive receptor.

Animals↗

Octopamine--after a decade as a putative neuroregulator.

From the above, it doesn't seem too rash now to elevate octopamine to the status of a neuroregulator in the invertebrates. To encapsulate, octopamine occurs in high concentration in many higher invertebrates and is found in specific octopaminergic neurons from which it is released upon stimulation. It then interacts with specific receptors, some of which at least, are linked to adenylate cyclase. The action of octopamine is then terminated by re-uptake or by N-acetylation (or a combination of these functions). It is fair to say we know as much about octopamine and its role as a neuromodulator in vertebrates as we do about noradrenaline in vertebrates-only our ignorance isn't as well documented. But where does octopamine fit into the scheme of Barchas et al. (1978)? We can agree that it is a neuroregulator but is it a neurotransmitter or a neuroregulator? Turning to the three well characterized octopaminergic systems, these all seem to be neuromodulatory in nature. Clearly the octopaminergic neurons in the lobster which release octopamine into the haemohymph fall into the neuromodulator class. In the case of the octopaminergic neurons in the adult firefly lantern, octopamine released from these neurons appears to interact with a specific adenylase cyclase-linked receptor and this leads to a response, the flash of the lantern. This therefore appears to be a situation where octopamine is a neurotransmitter, not dependent on other transmitters for actions (Nathanson, 1979). In the system of octopaminergic neurons which originate in the DUM neurons and innervate skeletal muscle, octopamine again appears to be a neuromodulator, altering the response of the muscle to another neurotransmitter (O'Shea and Evans, 1979). However, these peripheral octopaminergic system probably form only a small portion of the octopaminergic neurons in arthropods. The role of octopamine in the central nervous system must remain conjectural for the present.

Animals↗

Octopamine immunoreactivity in the fruit fly Drosophila melanogaster.

Octopamine has been proposed as a neurotransmitter/modulator/hormone serving a variety of physiological functions in invertebrates. We have initiated a study of octopamine in the fruit fly Drosophila melanogaster, which provides an excellent system for genetic and molecular analysis of neuroactive molecules. As a first step, the distribution of octopamine immunoreactivity was studied by means of an octopamine-specific antiserum. We focused on the central nervous system (CNS) and on the innervation of the larval body wall muscles. The larval octopamine neuronal pattern was composed of prominent neurons along the midline of the ventral ganglion, whereas brain lobes were devoid of immunoreactive somata. However, intense immunoreactive neuropil was observed both in the ventral ganglion and in the brain lobes. Some of the immunoreactive neurons sent peripheral fibers that innervated most of the muscles of the larval body wall. Octopamine immunoreactivity was observed at neuromuscular junctions in all larval stages, being present in a well-defined subset of synaptic boutons, type II. Octopamine immunoreactivity in the adult CNS revealed many additional neurons compared to the larval CNS, indicating that at least a subset of adult octopamine neurons may differentiate during metamorphosis. Major octopamine-immunoreactive neuronal clusters and neuronal processes were observed in the subesophageal ganglion, deutocerebrum, and dorsal protocerebrum, and intense neuropil staining was detected primarily in the optic lobes and in the central complex.

Animals↗

Effects of octopamine and forskolin on excitatory junction potentials of developing and adult moth muscle.

Intracellular recordings were made from the dorsal longitudinal muscle of Manduca sexta to determine the effects of development and octopamine on the excitatory junction potential (EJP) produced in response to electrical stimulation of the motor nerve. Observations were made on pharate moths during the last 3 days before eclosion and on adults. In saline, the highest values for EJP amplitude and maximum rate of rise and for resting membrane potential are reached on the nineteenth day of the pupal period, the day the animal ecloses; adult values are slightly lower. In animals of all ages tested, DL-octopamine (5 X 10(-6) M) increases EJP amplitude and maximum rate of rise. Increases in amplitude are greater in animals at stage day 17 and 18 than in animals at stage day 19 and adult. Octopamine has no effect on EJP rise time (onset to peak) or recovery time (peak of EJP to 70% recovery). Octopamine causes a hyperpolarization of about 6 mV. The results show that developmental changes in synapse properties are paralleled only in part by changes induced by octopamine. Both development and octopamine increase EJP amplitude and maximum rate of rise, and neither alter rise time. EJP recovery time changes with development but not in response to octopamine. Forskolin (10(-4) M) mimics the effects of octopamine on day 17 animals. EJP amplitude and maximum rate of rise are increased by forskolin, and rise time and recovery time are unaffected. Forskolin, like octopamine, causes a 6 mV hyperpolarization of the muscle fiber. These results suggest that octopaminergic modulation at the Manduca sexta dorsal longitudinal neuromuscular junction may be mediated by changes in intracellular levels of cyclic AMP.

Age Factors↗

Octopamine effects mimick state-dependent changes in a proprioceptive feedback system.

The modulatory actions of the biogenic amine octopamine on the femur tibia (FT) control loop in the stick insect Carausius morosus were examined. The response properties of the FT control loop were determined under open loop conditions. Mechanical stimulation of the femoral chordotonal organ (fCO) was the input and tibial movement and motoneuronal activity were measured as the output of the system. Following octopamine injection into the hemolymph of intact, inactive animals, two consecutive phases occurred at the behavioral level. Octopamine caused initially an activation of the animal. During this first phase (3.5-12 min duration) the response properties of the FT control loop were similar to those found in animals that were activated by tactile stimuli under normal conditions. Afterward, animals became inactive. During this second phase (15-20 min duration), the gain of the control loop was zero and no resistance reflex in the FT joint was generated in response to fCO stimulation. However, active movements of the tibia could still be elicited. As we could show in restrained animals, where DL-octopamine was applied topically onto the undesheated mesothoracic ganglion, the complete suppression of the resistance reflex on the motoneuronal level was dose dependent starting at concentrations of 5 x 10(-3) M octopamine. We could show that octopamine specifically suppressed the pathways involved in the resistance reflex, while feedback loop responses to fCO stimuli typical for active animals could still be elicited. Our results indicate that an increase in the octopamine concentration mimicks activation of the animal: Properties being characteristic for the control of the FT joint in the inactive animal are inhibited by octopamine, while properties of the FT control loop typical for the active animal appear to be facilitated following octopamine injection. The results clearly demonstrate that different pathways in the neuronal network underlying the FT control loop are involved in the responses of the control loop to fCO stimuli in the inactive and active behavioral states of the stick insect.

Animals↗

Octopamine relaxes rabbit jejunal smooth muscle by selective activation of dopamine D1 receptors.

The effect of octopamine on intestinal smooth muscle of rabbit isolated jejunum has been studied. Octopamine induced a dose-dependent decrease of muscle tone and this reproducible relaxation was not modified by tetrodotoxin or by agents that acted on adrenergic nerve terminals. Adrenoceptor antagonists, at concentrations sufficient to block each adrenoceptor type, did not reduce the actions of octopamine. On the other hand, octopamine-induced relaxations were affected by agents that have the ability to change cyclic AMP (cAMP) content; such as alloxan (an adenylate cyclase inhibitor), imidazole (a stimulator of phosphodiesterase), and isobutyl methylxanthine (an inhibitor of phosphodiesterase). Direct stimulation of adenylate cyclase by octopamine was demonstrated using radioimmunoassay of cAMP. Furthermore, haloperidol and perphenazine at concentration required to block dopamine receptor sites attenuated both smooth muscle relaxation and the formation of cAMP induced by octopamine. The effect of octopamine was totally blocked by SCH 23390, an antagonist of dopamine D-1 receptors. The lack of effect of domperidone and sulpiride, antagonists of dopamine D-2 receptors, on the actions of octopamine excludes the involvement of dopamine D-2 receptors. These results suggest that octopamine acts on intestinal dopamine D-1 receptor sites to produce relaxation of rabbit jejunum through an increase of cAMP.

Adenylyl Cyclases↗

Moderate weight-lowering effect of octopamine treatment in obese Zucker rats.

Octopamine is proposed as a substitution product of synephrine by diverse drug industries that advertise new weight-lowering products or medicinal plants enriched in this biogenic amine. We have already reported that octopamine is able to activate in vitro lipolysis in rat adipocytes via beta3-adrenergic receptor activation, while it activates glucose uptake in human fat cells via its oxidation by amine oxidases. In this work, we tested whether a chronic challenge with octopamine could exert anti-obesity effects. A treatment consisting in daily i.p. administration of octopamine (81 micromol/kg) was compared on a four-week period with calorie restriction in the genetically obese Zucker rat. Octopamine treatment resulted in a 19% decrease in body weight gain, when compared to the 177 g gained by controls during the same period. The decrease in body weight gain was detectable only after three weeks of treatment and was apparently not due to a pronounced and sustainable anorectic effect of octopamine since: 1) cumulated food consumption was only reduced by 10%; 2) the experimental 18% reduction of food intake provoked a rapid decrease in body weight gain, significant in less than two weeks. The lipolytic responses to isoprenaline or octopamine and the stimulation of glucose transport by insulin or by the amine oxidase substrate tyramine were unmodified by the treatments. Noteworthy, the elevated plasma insulin of obese rats was lowered by octopamine. This study shows that octopamine can reduce body weight gain in obese rats, without apparent adverse effects, but with less efficacy than beta3-AR agonists.

Adipocytes↗

Octopamine modulates spermathecal muscle contractions in Locusta migratoria.

Octopamine was identified in the spermathecal tissue of Locusta migratoria using HPLC and immunohistochemical techniques. Octopamine-like immunoreactive unpaired median neurons were identified in the VIIth and VIIIth (terminal) abdominal ganglia and octopamine-like immunoreactive axons were present in the ventral ovipositor nerve (branches from this nerve innervate the spermatheca). Stimulatory actions of octopamine on myogenic and neurogenic contractions were observed. Dose-dependent increases in the frequency of myogenic contractions and the amplitude of neurogenic contractions were elicited by the application of octopamine to the spermathecal muscle. Non-sustained basal tension increases were noted in some preparations, although these were not found to be dose-dependent. SchistoFLRFamide (PDVDHVFLRFamide) inhibited octopamine-induced contractions by a maximum of about 30%. In the presence of 3-isobutyl-1 -methylxanthine, octopamine increased cAMP levels in all regions of the spermathecal. The largest increase in cAMP content was found in the spermathecal sac, followed by the straight duct and coil duct. Phentolamine blocked octopamine-induced increases in cAMP levels and abolished the actions of octopamine on myogenic contractions.

1-Methyl-3-isobutylxanthine↗

Selective modulation of task performance by octopamine in honey bee (Apis mellifera) division of labour.

Octopamine treatment has previously been shown to increase honey bee foraging behaviour. We determined the effects of octopamine on other tasks to learn how octopamine affects division of labour in honey bee colonies. Octopamine treatment did not increase the rate of corpse removal from the hive, suggesting that elevated brain levels of octopamine do not act to increase the performance of all flight-related tasks. Octopamine treatment also did not increase attendance in the queen's retinue, suggesting that elevated brain levels of octopamine do not act to increase responsiveness to all olfactory stimuli. Consistent with these findings, octopamine treatment enhanced the foraging response to brood pheromone but not the cell capping response, a component of brood care. These results demonstrate a relatively specific form of neuromodulation by octopamine in the regulation of division of labour in honey bee colonies.

Animals↗

Octopamine influences division of labor in honey bee colonies.

Forager honey bees have higher brain levels of octopamine than do bees tending larvae in the hive. To test the hypothesis that octopamine influences honey bee division of labor we treated bees orally with octopamine or its immediate precursor tyramine and determined whether these treatments increased the probability of initiating foraging. Octopamine treatment significantly elevated levels of octopamine in the brain and caused a significant dose-dependent increase in the number of new foragers. This effect was seen for precocious foragers in single-cohort colonies and foragers in larger colonies with more typical age demographies. Tyramine treatment did not increase the number of new foragers, suggesting that octopamine was exerting a specific effect. Octopamine treatment was effective only when given to bees old enough to forage, i.e., older than 4 days of age. Treatment when bees were 1-3 days of age did not cause a significant increase in the number of new foragers when the bees reached the minimal foraging age. These results demonstrate that octopamine influences division of labor in honey bee colonies. We speculate that octopamine is acting in this context as a neuromodulator.

Adrenergic alpha-Agonists↗

The release of octopamine and proctolin from an insect visceral muscle: effects of high-potassium saline and neural stimulation.

The release of octopamine and proctolin from the oviduct visceral muscles of the locust, Locusta migratoria, has been investigated. Salines containing elevated potassium concentrations (100 mM) were capable of releasing both octopamine and proctolin, although the proportion of the total store of octopamine released (19%) was much greater than that of proctolin (0.4%). The high potassium-induced release of octopamine was calcium-dependent. Electrical stimulation of the oviducal nerves also resulted in the release of octopamine and proctolin. The release of both substances was frequency-dependent with maximum release of octopamine occurring at about 5 Hz, and maximum release of proctolin at 30 Hz. Neural stimulation was a more effective means of inducing proctolin release than was high-potassium saline, with 6.3% of the total store of proctolin released with 5 min stimulation at 30 Hz. The neurally stimulated release of proctolin was calcium-dependent. In addition, intrasomatic stimulation of the octopaminergic neurons which project to the oviducts resulted in the release of octopamine. The results clearly indicate that both octopamine and proctolin, which have previously been shown to be associated with locust oviducts, are released in a calcium-dependent manner by physiological stimuli. This strengthens the case for octopamine and proctolin as natural regulators of this insect visceral muscle.

Animals↗

Cloning, expression and functional analysis of an octopamine receptor from Periplaneta americana.

Octopamine regulates multiple physiological functions in invertebrates. The biological effects of octopamine and the pharmacology of octopamine receptors have been extensively studied in the American cockroach, Periplaneta americana. This paper reports the cloning of the first octopamine receptor from Periplaneta americana. A cDNA encoding a putative 7 transmembrane receptor was isolated from the head of Periplaneta americana. The encoded protein contains 628 amino acids and has sequence similarity to other biogenic amine receptors. This protein was expressed in COS-7 cells for radioligand binding studies using the antagonist 3H-yohimbine. Competitive binding comparing biogenic amines that could potentially function as endogenous ligands demonstrated this receptor had the highest affinity for octopamine (Ki = 13.3 microM) followed by tyramine, dopamine, serotonin and histamine. Octopamine increased both cAMP levels (EC50 = 1.62 microM) and intracellular concentrations of calcium through the receptor expressed in HEK-293 cells. Tyramine increased levels of both of these second messengers but only at significantly higher concentrations than octopamine. The cAMP increase by octopamine was independent of the increase in calcium. Competitive binding with antagonists revealed this receptor is similar to Lym oa1 from Lymnaea stagnalis. The data indicate that this cDNA is the first octopamine receptor cloned from Periplaneta americana and therefore has been named Pa oa1.

Amino Acid Sequence↗

Inhibitory effect of octopamine on the release of endogenous acetylcholine from isolated myenteric synaptosomes of guinea-pig.

1. The effect of octopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal preparations of guinea-pigs was examined using high pressure liquid chromatography with electrochemical detection. Release of ACh was induced by substance P or by depolarization with high potassium (50 mmol/L) in medium containing atropine, propranolol and naloxone. 2. Octopamine produced a dose-dependent inhibition of substance P-induced ACh release. A similar inhibitory action of octopamine was found in the samples depolarized by high potassium as a reference. 3. The action of octopamine was not reversed by the dopamine receptor antagonists either for the DA-2 subtype, domperidone, or for the DA-1 subtype, SCH23390, or by haloperidol. However, idazoxan and yohimbine antagonized this octopamine-induced inhibition at concentrations sufficient to abolish the action of clonidine. 4. Failure of guanethidine or nomifensine to inhibit octopamine ruled out mediation by noradrenergic neurotransmitters. 5. Octopamine decreased the influx of [45Ca] stimulated by substance P into synaptosomal preparations and this was reversed by idazoxan or yohimbine at concentrations sufficient to block the action of clonidine. 6. Pertussis toxin abolished the inhibitory action of octopamine at a dose high enough to block the action of clonidine. 7. These results indicate that octopamine suppresses the influx of calcium ions into cholinergic nerve terminals of ileal synaptosomes of guinea-pigs via an activation of alpha 2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein which results in a decrease of ACh release.

Acetylcholine↗

Octopamine increases the excitability of neurons in the snail feeding system by modulation of inward sodium current but not outward potassium currents.

BACKGROUND: Although octopamine has long been known to have major roles as both transmitter and modulator in arthropods, it has only recently been shown to be functionally important in molluscs, playing a role as a neurotransmitter in the feeding network of the snail Lymnaea stagnalis. The synaptic potentials cannot explain all the effects of octopamine-containing neurons on the feeding network, and here we test the hypothesis that octopamine is also a neuromodulator. RESULTS: The excitability of the B1 and B4 motoneurons in the buccal ganglia to depolarising current clamp pulses is significantly (P < < 0.05) increased by (10 microM) octopamine, whereas the B2 motoneuron becomes significantly less excitable. The ionic currents evoked by voltage steps were recorded using 2-electrode voltage clamp. The outward current of B1, B2 and B4 motoneurons had two components, a transient IA current and a sustained IK delayed-rectifier current, but neither was modulated by octopamine in any of these three buccal neurons. The fast inward current was eliminated in sodium-free saline and so is likely to be carried by sodium ions. 10 microM octopamine enhanced this current by 33 and 45% in the B1 and B4 motoneurons respectively (P < < 0.05), but a small reduction was seen in the B2 neuron. A Hodgkin-Huxley style simulation of the B1 motoneuron confirms that a 33% increase in the fast inward current by octopamine increases the excitability markedly. CONCLUSION: We conclude that octopamine is also a neuromodulator in snails, changing the excitability of the buccal neurons. This is supported by the close relationship from the voltage clamp data, through the quantitative simulation, to the action potential threshold, changing the properties of neurons in a rhythmic network. The increase in inward sodium current provides an explanation for the polycyclic modulation of the feeding system by the octopamine-containing interneurons, making feeding easier to initiate and making the feeding bursts more intense.

Animals↗