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PubMed1986

Identified octopaminergic neurons modulate contractions of locust visceral muscle via adenosine 3',5'-monophosphate (cyclic AMP).

D,L-Octopamine elevates the cyclic AMP content of the lateral oviduct of the locust, Locusta migratoria, in a dose-dependent manner with a threshold of about 10(-8) M. The effect of octopamine is potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The response is specific for octopamine and synephrine with an order of potency being octopamine = synephrine greater than metanephrine greater than tyramine greater than norepinephrine = dopamine = 5-hydroxytryptamine and the effect of octopamine is inhibited by the alpha-adrenergic receptor antagonist phentolamine. The diterpene adenylate cyclase activator forskolin also elevates cyclic AMP levels and IBMX potentiates the action of forskolin. Stimulation of the two identified octopaminergic neurons which project to the lateral oviducts results in an elevation in cyclic AMP and again this effect is blocked by phentolamine. Elevation of cyclic AMP levels in the lateral oviducts by means of IBMX, forskolin or dibutyryl cyclic AMP mimics the physiological effects of octopamine on this preparation. The results indicate that the octopaminergic control of this insect's visceral muscle is mediated via cyclic AMP.

1-Methyl-3-isobutylxanthine↗
PubMed1987

Regulation of adipokinetic hormone release from locust neuroendocrine tissue: participation of calcium and cyclic AMP.

In the locust, cyclic adenosine monophosphate (cAMP) mediates at least part of the effects of octopamine, the neurotransmitter which regulates the release of two adipokinetic hormones (AKHs) from the glandular lobe of the corpus cardiacum (CC). We have examined the requirement for extracellular Ca2+ in the process of AKH release mediated by octopamine and by agents which artificially elevate intracellular cAMP levels. Octopamine and the adenylate cyclase activator forskolin elevate the cAMP content of the glandular lobe in normal saline, in normal saline with the Ca2+ channel blocker, methoxyverapamil, and in Ca2+-free saline during 10-min exposure periods. Octopamine, forskolin, and 8-bromo cAMP mediate release of AKHs in vitro in normal saline, but release is prevented in the absence of extracellular Ca2+. When glands are exposed to these agents in normal saline in the presence of methoxyverapamil, AKH release is curtailed in a similar manner. Lanthanum and EGTA dramatically reduce cAMP production elicited by octopamine and forskolin, and lanthanum prevents octopamine-mediated release of AKHs. The phosphodiesterase inhibitor, IBMX, elevates cAMP content in the presence and absence of extracellular Ca2+, and stimulates normal release of AKHs both in the presence and absence of extracellular Ca2+. However, following extensive washing in Ca2+-free saline, IBMX fails to evoke AKH release. Methoxyverapamil has no effect on IBMX-mediated secretion. These results suggest that IBMX may mobilize intracellular stores of Ca2+ to induce release. Extracellular Ca2+ is apparently required for the process of neurotransmitter-evoked release, as has been shown for release of other peptide hormones. Cyclic AMP is intimately associated with Ca2+ in mediating this process. The release of AKHs is more dependent upon extracellular Ca2+ than is cAMP production under the conditions examined in this study. Ca2+ may provide the signal which initiates the secretory response, although cAMP may modulate this signal or the cells' responsiveness to this signal in some way. Support for this hypothesis is provided by experiments with the Ca2+ ionophore, A23187. This agent provokes release of AKHs in a Ca2+-dependent manner, probably by elevating intracellular Ca2+ levels. A23187 does not elevate cAMP levels in the glandular lobe, indicating that cAMP elevation is not a prerequisite for secretion.

1-Methyl-3-isobutylxanthine↗
PubMed1982

Antagonistic responses of the radular protractor and retractor to the same putative neurotransmitters.

1. Mechanisms of antagonistic responses of the radular protractor and the retractor to the same neurotransmitters, octopamine and serotonin, were investigated in a mollusc, Rapana thomasiana. 2. Hyperpolarization induced by octopamine or serotonin was found to depend mainly on the increase in Cl- conductance of the membrane in both the radular protractor and the retractor. 3. In the protractor, the enhancement of acetylcholine depolarization during the application of octopamine or serotonin was exhibited even when the membrane potential was varied by current application. Spontaneous firing was blocked by these amines, but larger spikes with higher frequency were elicited on giving a depolarizing current above threshold. 4. In the retractor, the inhibition of glutamate depolarization during the application of octopamine or serotonin was observed irrespective of membrane potential. Spontaneous spikes were stopped by these amines but reappeared on depolarization above threshold. Reappeared spikes during serotonin application were smaller than control spikes, while those during octopamine application were about the same as or larger than control ones. 5. The modes of actions of octopamine and serotonin on both muscles were considered.

Acetylcholine↗
PubMed2004

Tyramine receptor (SER-2) isoforms are involved in the regulation of pharyngeal pumping and foraging behavior in Caenorhabditis elegans.

Octopamine regulates essential processes in nematodes; however, little is known about the physiological role of its precursor, tyramine. In the present study, we have characterized alternatively spliced Caenorhabditis elegans tyramine receptor isoforms (SER-2 and SER-2A) that differ by 23 amino acids within the mid-region of the third intracellular loop. Membranes prepared from cells expressing either SER-2 or SER-2A bind [3H]lysergic acid diethylamide (LSD) in the low nanomolar range and exhibit highest affinity for tyramine. Similarly, both isoforms exhibit nearly identical Ki values for a number of antagonists. In contrast, SER-2A exhibits a significantly lower affinity than SER-2 for other physiologically relevant biogenic amines, including octopamine. Pertussis toxin treatment reduces affinity for both tyramine and octopamine, especially for octopamine in membranes from cells expressing SER-2, suggesting that the conformation of the mid-region of the third intracellular loop is dictated by G-protein interactions and is responsible for the differential tyramine/octopamine affinities of the two isoforms. Tyramine reduces forskolin-stimulated cAMP levels in HEK293 cells expressing either isoform with nearly identical IC50 values. Tyramine, but not octopamine, also elevates Ca2+ levels in cells expressing SER-2 and to a lesser extent SER-2A. Most importantly, ser-2 null mutants (pk1357) fail to suppress head movements while reversing in response to nose-touch, suggesting a role for SER-2 in the regulation of foraging behavior, and fail to respond to tyramine in assays measuring serotonin-dependent pharyngeal pumping. These are the first reported functions for SER-2. These results suggest that C. elegans contains tyramine receptors, that individual SER-2 isoforms may differ significantly in their sensitivity to other physiologically relevant biogenic amines, such as octopamine (OA), and that tyraminergic signaling may be important in the regulation of key processes in nematodes.

Adrenergic Uptake Inhibitors↗
PubMed1991

Octopaminergic modulation of interneurons in the flight system of the locust.

1. Modulatory effects of octopamine perfusion on identified central neurons in the flight system of the locust Locusta migratoria were examined by means of intracellular recordings from the isolated metathoracic ganglion. 2. Octopamine increased the excitatory response of elevator motoneurons to electrical stimulation of the hindwing tegula and increased the probability of triggering rhythmic activity in the flight system by current injection into single interneurons. 3. These effects of octopamine on the flight system are due in part to octopamine inducing intrinsic bursting properties in flight interneurons. Plateau potentials were evoked in these interneurons by synaptic input from tegula or by the injection of depolarizing current pulses. These potentials were prematurely terminated by hyperpolarizing currents, and their generation was voltage sensitive in that they were suppressed with hyperpolarizing offset currents. 4. Longer depolarizing current pulses evoked endogenous bursting in a number of flight interneurons. This rhythmic bursting was reset by the injection of pulses of hyperpolarizing currents. The frequency of bursting was dependent on the injected current strength. 5. The injection of hyperpolarizing current into flight interneurons during octopamine-induced rhythmic activity lead to sudden decreases in the amplitude of the depolarizations thus indicating that plateau potentials contribute to the generation of the rhythmic depolarizations. 6. The shape of the depolarizations, the duration of the bursts (50-75 ms), and the frequency range of endogenous bursting (4-16 Hz) as seen in individual interneurons during octopamine perfusion were similar to the corresponding characteristics in the same neurons during wind-induced flight activity in deafferented locusts. This correspondence suggests that intrinsic bursting properties may play an important role in generating the normal motor pattern for flight.

Animals↗
PubMed1986

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

The actions of octopamine on the Schwann cells of the giant nerve fibre of the tropical squid are described. The pharmacology of the receptors mediating the actions of octopamine has been investigated in terms of stereospecificity, amine specificity and interactions with a range of agonists and antagonists. The receptors are maximally activated by D(-)-octopamine and share many of the characteristics of OCTOPAMINE2 class receptors in other preparations. The octopamine receptors appear to mediate their actions by increasing the intracellular levels of cyclic AMP in the Schwann cells. Low concentrations of octopamine potentiate the actions of the nicotinic cholinergic activation system of the Schwann cells. The results are discussed in terms of the possible physiological role of octopamine in the modulation of Schwann cell activity during stressful conditions when the giant axon system is likely to be used at a high frequency to facilitate the escape response of the squid.

Amines↗
PubMed1996

Anatomy and targets of Dorsal Unpaired Median neurones in the Terminal Abdominal Ganglion of the male cockroach Periplaneta americana L.

The morphology of the Dorsal Unpaired Median (DUM) neurones in the Terminal Abdominal Ganglion (TAG) of the adult male cockroach Periplaneta americana were described based on wholemount preparations and paraffin sections and by using anterograde and retrograde cobalt mapping, octopamine-like immunohistochemistry, and double immunofluorescence technique with both conjugated gamma-aminobutyric acid (GABA) and octopamine antisera. Among 60 +/- 6 neurones with large somata (diameter 40 to 60 microns) on the dorsal midline surface of the TAG that were stained with toluidine blue, about 36 efferent DUM neurones exhibited octopamine-like immunoreactivity. The DUM neurones were arranged in three clusters (anterior, median and posterior) corresponding to the 7th-11th abdominal ganglia of the fused TAG. Anterior efferent DUM neurones with one, two, and four pairs of lateral neurites entered segmental nerves VIIB; VIIB and phallic nerves; IXB and phallic nerves; VIIIA, IXA, X, and IX, respectively. Three octopamine-like immunoreactive DUM neurones innervating heart chambers via segmental nerves (VIIA, VIIIA, and IXA) in the last abdominal segments occurred within abdominal ganglia 7, 8, and 9. Together with octopamine-like immunoreactive efferent DUM neurones, GABA-like immunoreactive dorsal midline neurones with small somata (10 to 20 microns) also occurred within the median group. The spatial distribution of DUM neurones in the TAG suggested that they had their origins in the median neuroblast, as for DUM neurones in the grasshopper.

Abdomen↗
PubMed2003

Biogenic amines in the antennal lobes and the initiation and maintenance of foraging behavior in honey bees.

Previous findings showed that high levels of octopamine and serotonin in the antennal lobes of adult worker honey bees are associated with foraging behavior, and octopamine treatment induces precocious foraging. To better characterize the relationship between amines and foraging behavior in honey bees, we performed a detailed correlative analysis of amine levels in the antennal lobes as a function of various aspects of foraging behavior. Flight activity was measured under controlled conditions in a large outdoor flight cage. Levels of octopamine in the antennal lobes were found to be elevated immediately subsequent to the onset of foraging, but they did not change as a consequence of preforaging orientation flight activity, diurnal pauses in foraging, or different amounts of foraging experience, suggesting that octopamine helps to trigger and maintain the foraging behavioral state. In contrast, levels of serotonin and dopamine did not show changes that would implicate them as either causal agents of foraging, or as neurochemical systems affected by the act of foraging. Serotonin treatment had no effect on the likelihood of foraging. These results provide further support for the hypothesis that an increase in octopamine levels in the antennal lobes plays a causal role in the initiation and maintenance of the behavioral state of foraging, and thus is involved in the regulation of division of labor in honey bees.

5-Hydroxytryptophan↗
PubMed1999

Biogenic amines and division of labor in honey bee colonies.

Brain levels of dopamine, serotonin, and octopamine were measured in relation to both age-related division of labor and inter-individual differences in task specialization independent of age in honey bee colonies. The only differences among similarly aged bees performing different tasks were significantly lower levels of dopamine in food storers than comb builders and significantly lower levels of octopamine in soldiers than foragers, but soldiers also were slightly younger than foragers. Differences associated with age-related division of labor were stronger. Older bees, notably foragers, had significantly higher levels of all three amines than did younger bees working in the hive. Using social manipulations to unlink chronological age and behavioral status, octopamine was found to exhibit the most robust association between behavior and amine level, independent of age. Octopamine levels were significantly lower in normal-age nurses versus precocious foragers and overage nurses versus normal-age foragers, but not different in reverted nurses versus reversion colony foragers. Dopamine levels were significantly lower in normal-age nurses versus precocious foragers, but higher in reverted nurses versus reversion colony foragers. Serotonin levels did not differ in any of these comparisons. These correlative results suggest that octopamine is involved in the regulation of age-related division of labor in honey bees.

Aging↗
PubMed1983

Pharmacology of aminergic receptors mediating an elevation in cyclic AMP and release of hormone from locust neurosecretory cells.

Synaptic activation of the neurosecretory cells within the glandular lobe of the corpus cardiacum of locusts results in the release of bioassayable adipokinetic hormones and an elevation in cAMP. The effectiveness of several putative aminergic neurotransmitters in mimicking these actions of the natural transmitter, and the effects of aminergic antagonists, have been studied. The receptors mediating the release of adipokinetic hormones exhibited a specificity for the monophenolic amines octopamine and synephrine at 10(-7) M. These two amines were also the most effective, at 5 X 10(-6) M, in elevating cAMP levels. Octopamine induced a dose-dependent elevation in cAMP with half-maximal stimulation occurring at 5 X 10(-6) M. 5-Hydroxytryptamine (5-HT) was also capable of elevating cAMP levels, but, unlike the octopamine response, or the response to the natural transmitter, the response to 5-HT was not blocked by the antagonist phentolamine. Gramine was also an effective antagonist of the octopamine-induced response. The results are consistent with the hypothesis that octopamine is the natural transmitter within this neurosecretory system.

Animals↗
PubMed1987

Pharmacological characterisation of the dopamine-sensitive adenylate cyclase in cockroach brain: evidence for a distinct dopamine receptor.

Dopamine increases cyclic AMP production in crude membrane preparations of cockroach brain with plateaus in cyclic AMP production occurring between 1-10 microM and at 10 mM. Maximal production of cyclic AMP is 2.25 fold greater than that of control values. Octopamine also increases cyclic AMP production with a Ka of 1.4 microM and maximal production 3.5 fold greater than that of control. 5-Hydroxytryptamine does not increase cyclic AMP production. The effects of octopamine and dopamine are fully additive. The vertebrate dopamine agonists ADTN and epinine stimulate the dopamine-sensitive adenylate cyclase (AC) with Ka values of 4.5 and 0.6 microM respectively and with maximal effectiveness 1.7 fold greater than that of control. The selective D2-dopamine agonist LY-171555 stimulates cyclic AMP production to a similar extent with a Ka of 50 microM. Other dopamine agonists (apomorphine, SKF-82526, SKF-38393) have no stimulatory effects. The octopamine-sensitive AC is inhibited by a variety of antagonists known to affect octopamine and dopamine receptors, with the following order of potency: mianserin greater than phentolamine greater than cyproheptadine greater than piflutixol greater than cis-flupentixol greater than SCH-23390 greater than (+)-butaclamol greater than SKF-83566 greater than SCH-23388 greater than sulpiride greater than spiperone greater than haloperidol. The dopamine-sensitive AC is inhibited by the same compounds with the following order of potency: piflutixol greater than cis-flupentixol greater than (+)-butaclamol greater than spiperone greater than or equal to SCH-23390 greater than cyproheptadine greater than SKF-83566 greater than SCH 23388 greater than mianserin greater than phentolamine greater than sulpiride greater than haloperidol. With the exception of mianserin, 3H-piflutixol is displaced from brain membranes by dopamine antagonists with an order of potency similar to that observed for the inhibition of dopamine-sensitive AC. The results indicate that the octopamine- and dopamine-sensitive AC in cockroach brain can be distinguished pharmacologically and the dopamine receptors coupled to AC have pharmacological characteristics distinct from vertebrate D1- and D2-dopamine receptors.

Adenylyl Cyclases↗
PubMed2002

A trace amine, tyramine, functions as a neuromodulator in Drosophila melanogaster.

The tyramine receptor (TyrR) is a G protein-coupled receptor for trace amines, cloned in Drosophila melanogaster, and claimed to be either an octopamine receptor or a tyramine receptor. We previously reported that in the larval neuromuscular junctions, the modulatory effect on the excitatory junction potentials of tyramine is distinctly different from that of octopamine. The effect of tyramine but not of octopamine was selectively abolished in the TyrR mutant hono, suggesting that this gene encodes a receptor for tyramine, and not for octopamine. We examined whether there was a gene-dosage effect of this tyramine modulation using combinations of hono, deficiency (Df) and wild-type alleles. The tyramine effect was observed in hono heterozygotes (+/hono), which showed intermediate levels of response, but was not seen in +/Df or hono/Df hemizygotes. While these further suggest that tyramine is the true ligand, it is possible that the gene-dosage effect is only evident above some threshold of gene expression levels. Immunohistochemical staining using an anti-tyramine antibody identified tyramine-containing neurons in the larval central nervous system, some of which were distinct from the octopamine-containing neurons. Taken together, these results strongly suggest that tyramine functions as a neuromodulator.

Animals↗
PubMed2003

Site-directed mutagenesis studies on the Drosophila octopamine/tyramine receptor.

The cloned Drosophila octopamine/tyramine receptor can be coupled to second messenger pathways in an agonist-specific fashion by the endogenously occurring biogenic amines, octopamine and tyramine, when expressed in Chinese hamster ovary cells. We have mutated to alanine a range of receptor amino acids that could potentially form hydrogen bonds with the beta-hydroxyl group of octopamine based on homologies with alpha- and beta-adrenergic receptor subtypes. After stable expression of the mutant receptors in CHO cells we have compared the ability of octopamine and tyramine to displace [(3)H]yohimbine binding to membrane fractions from the mutant cell lines with their ability to modulate adenylyl cyclase activity in intact cells. The results suggest that none of the mutated amino acids residues, at least in isolation, are likely to be involved in interactions with the beta-hydroxyl group of the octopamine side chain. It is possible that amino acids not mutated in the present study are somehow involved in this interaction. Alternatively, it is also possible that the beta-hydroxyl group of the octopamine side chain is capable of interacting with more than one of the amino acids mutated in the present study.

Amino Acid Substitution↗
PubMed1982

Aminergic receptors in Drosophila melanogaster: responsiveness of adenylate cyclase to putative neurotransmitters.

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

Adenylyl Cyclases↗
PubMed1986

Veratridine-stimulated release of amine conjugates from centrifugal fibers in the Limulus peripheral visual system.

Centrifugal fibers that originate in the brain and project to the Limulus peripheral visual system synthesize and store octopamine and conjugates of octopamine and tyramine. In a previous study we showed that depolarization, induced by elevating extracellular K+, stimulated a preferential release of octopamine from these fibers. Here we show that veratridine-induced depolarization stimulates a rapid, transient release of octopamine and a delayed, sustained release of amine conjugates. Veratridine-stimulated release of both octopamine and amine conjugates depends on the influx of extracellular Ca2+ and is blocked by tetrodotoxin or the absence of extracellular Na+. The depolarization-stimulated release of amine conjugates raises the possibility that these molecules serve as intercellular messengers in the Limulus peripheral visual system.

Amines↗
PubMed1980

Effects of molindone and fluphenazine on the brain concentration of some phenolic and catecholic amines in the mouse and the rat.

1 The concentrations of p- and m-tyramine, dopamine, 3,4-dihydroxyphenylacetic acid and homo-vanillic acid were measured in the mouse or rat striatum following the subcutaneous injection of molindone or fluphenazine. The mouse hypothalamic levels of the m- or p-isomers of octopamine were also analysed. 2 Endogenous concentrations of p- and m-tyramine in the mouse striatum and p- and m-octopamine in the mouse hypothalamus were 20.6, 5.7, 9.4 and 1.2 ng/g respectively. The rat striatum concentrations of p- and m-tyramine were 12.8 and 3.8 ng/g. 3 The administration of low doses of molindone (1 to 10 mg/kg) produced a reduction in striatal p-tyramine, an increase in m-tyramine and an increase in dopamine turnover. Similar effects were produced by all doses of fluphenazine (0.1 to 5 mg/kg) employed. These findings are consistent with those observed after blockade of dopamine postsynaptic receptors. 4 With high doses of molindone (100 mg/kg) the effects on both tyramines and on dopamine metabolism were reversed. These results can be interpreted as molindone acting as a partial agonist. 5 The concentrations of hypothalamic p- and m-octopamine were increased by the higher doses of molindone (20 to 100 mg/kg) employed while lower doses produced no significant effects. All doses of fluphenazine reduced hypothalamic p-octopamine. These changes seem to depend on differences in the availability of p-tyramine to be converted into p-octopamine. 6 These results suggest that molindone acts as a blocker or a partial agonist of dopamine receptor sites and fit well with the proposal of a reciprocal relation between dopamine and tyramine. It is not possible yet to ascertain whether tyramine controls dopamine or vice versa or if it is a direct or a more remote relation.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

Initial catabolism of aromatic biogenic amines by Pseudomonas aeruginosa PAO: pathway description, mapping of mutations, and cloning of essential genes.

Pseudomonas aeruginosa PAO1 was able to utilize several aromatic biogenic amines as sole sources of carbon or nitrogen. These included the phenethylamines tyramine and dopamine and the phenethanolamines octopamine, synephrine, and norepinephrine. Initial catabolism of the phenethylamines was mediated by a membrane-bound tyramine dehydrogenase which produced 4-hydroxyphenylacetaldehyde (4HPAL) with tyramine as the substrate. The enzyme was induced by growth with both classes of amines. Initial catabolism of octopamine (except when present as the sole source of carbon and nitrogen) was mediated by a soluble enzyme with activity against the phenethanolamines but not against tyramine or dopamine. The product of the reaction with octopamine as substrate was also 4HPAL. Addition of NAD to reaction mixtures yielded 4-hydroxyphenylacetic acid and NADH. These activities, octopamine hydrolyase and 4-HPAL dehydrogenase (measured as a combined activity, OCAH-4HPALDH), were only induced by growth with phenethanolamines. However, the combined activities were not observed in extracts from cells grown with octopamine as the sole source of carbon and nitrogen, suggesting that an alternate pathway is used under this growth condition. Two independently isolated mutant strains were unable to utilize tyramine as a sole source of carbon or nitrogen. These mutants were also unable to utilize dopamine but grew at wild-type rates on the phenethanolamines. The mutations were mapped at about 70 min on the PAO1 chromosome with the chromosome-mobilizing plasmid R68.45, and both were linked to the catA1, mtu-9002, tyu-9009, and puuE mutations. DNA complementing both of the mutations was cloned on a single BamHI fragment approximately 13.8 kilobase pairs in length. Analysis of a subcloned fragment showed that the two mutations were in different genes.

Biogenic Amines↗
PubMed1994

Modulating a modulator: biogenic amines at subthreshold levels potentiate peptide-mediated cardioexcitation of the heart of the tobacco hawkmoth Manduca sexta.

The central nervous system of the moth Manduca sexta contains a group of myoregulatory neuropeptides, the CAPs (Cardioacceleratory Peptides), which cause a physiologically important, dose-dependent increase in heart rate during wing inflation and flight in adult moths. We report here that the response of the adult heart to a subset of the CAPs, the CAP2S, is potentiated nearly twofold in the chronic presence of subthreshold levels of the biogenic amine octopamine or near-threshold levels of the biogenic amine serotonin. Subthreshold levels of the CAP2S fail to alter the response of the heart to octopamine. We have begun to investigate the molecular mechanisms underlying this potentiation. Previous work on the adult heart has shown that the CAP2s act through an inositol-1,4,5-trisphosphate second-messenger system. Here, we demonstrate that the cardioexcitatory effects of the two amines, in contrast to those of the CAP2S, are both mediated by cyclic AMP. Application to the heart of either 10(-5) moll-1 octopamine or 10(-6)moll-1 serotonin elicits a threefold increase in intracellular cyclic AMP levels. The CAP2S have no effect on cyclic AMP levels in the heart. These results illustrate a mechanism by which the effectiveness of a neurohormone can be increased with minimal cost to the animal. In Manduca sexta, subthreshold levels of octopamine are found in the haemolymph during wing inflation and flight. Thus, it is possible that octopamine up-regulates the effects of CAP2 via a cyclic-AMP-dependent mechanism during these activities.

Animals↗