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The association of octopamine with specific neurones along lobster nerve trunks.

Octapamine and its synthetic enzyme, tyramine beta-hydroxylase (TBH), are found in high concentrations at two points along second thoracic nerve roots in lobsters. The first is in the proximal section of the second root between the ventral nerve cord and the bifurcation of the root into medial (to flexor muscles) and lateral (to extensors) branches. The second region of high concentration is within a well known crustacean neurosecretory system, the pericardial organ, located close to the ends of the lateral branches of the roots. 2. With several different staining procedures, small clusters of nerve cell bodies are found within the connective tissue sheath in the proximal regions of the second roots. No cell bodies are seen in the pericardial organ regions. Cell bodies are variable in number and position between corresponding roots in the same animal and homologous roots among different animals. The average numbers of cell bodies, however, correlate well with TBH and octopamine content, and with the synthesis of octopamine in these same regions of roots. 3. Small clusters of root cell bodies dissected from preparations have greater than 500-fold higher activities of TBH than isolated efferent excitatory and inhibitory or afferent sensory axons. 4. Along with octopamine, the preferential synthesis of acetylcholine and serotonin is also seen in proximal segments of roots. Acetylcholine synthesis in these regions may represent transmitter synthesized in the nerve terminals innervating the root cells. The role of serotonin in these regions is not understood at this time but the amounts of endogenous serotonin found are only a tenth of the amounts of octopamine present. 5. Dopamine is not synthesized from tyrosine in second thoracic roots. However, if DOPA or dopamine are used as precursor compounds, then noradrenaline, which is usually not found in lobsters, can be accumulated in proximal segments of roots. 6. Phenolamines are converted to two further metabolites by lobster tissues. The compounds are unidentified and are named fast and slow product on the basis of their migration on electrophoresis at acid pH. Some partial characterization of slow product reveals that it is a mixture of compounds that can be converted on mild acid hydrolysis to fast product and the parent phenolamine. 7. The several lines of evidence presented suggest that nerve cells found in the proximal segments of the second thoracic roots contain and can synthesize octopamine. Since not all the cells in any single root have been analysed for octopamine or TBH, however, the possibility that one or more of the cells contain physiologically interesting substances other than octopamine is not eliminated.

Animals↗

Modulation of the crayfish swimmeret rhythm by octopamine and the neuropeptide proctolin.

1. The swimmeret system can be excited by perfusing the neuropeptide proctolin through the isolated ventral nerve cord of the crayfish. Previously silent preparations begin to generate a characteristic motor pattern, the swimmeret rhythm, in the nerves that innervate the swimmerets. The response to proctolin is dose dependent and reversible. The threshold concentration of proctolin perfused through the ventral artery is approximately 10(-8) M. The EC50 is 1.6 X 10(-6) M. 2. Proctolin-induced motor patterns have periods and phases similar to those of spontaneously generated motor patterns. The durations of the bursts of impulses in power-stroke motor neurons generated in the presence of proctolin are, however, significantly longer than those that occur during spontaneous activity. 3. DL-Octopamine inhibits the swimmeret system, both when the system is spontaneously active and when it has been excited by proctolin. The inhibition by octopamine is dose dependent and reversible. The threshold for inhibition is approximately 10(-6) M, and the EC50 is approximately 5 X 10(-5) M. 4. Octopamine's effect is mimicked by its agonists, synephrine and norepinephrine. Synephrine has a lower threshold concentration than does octopamine, but norepinephrine is much less effective than octopamine. 5. Octopamine's inhibition is partially blocked by an antagonist, phentolamine. 6. Phentolamine also blocks inhibition of the swimmeret system by inhibitory command interneurons. This block is dose dependent and can be partially overcome by stimulating the command interneurons at higher frequencies. 7. Perfusion with 11 other suspected crustacean neurotransmitters and transmitter analogues did not similarly excite or inhibit the swimmeret system, so we suggest that proctolin and octopamine are transmitters used by the neurons that normally control expression of the swimmeret rhythm.

Animals↗

Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases.

Octopamine, which is closely related to norepinephrine, acts as a neurotransmitter in invertebrates and is a trace amine with undefined properties in vertebrates. The octopaminergic receptors identified in insects are targets of various pesticides but are absent in vertebrates. We have established that octopamine stimulates fat cell lipolysis in mammals via activation of beta3-adrenoceptors (ARs), whereas this amine has been described elsewhere as an alpha2-AR agonist and as a substrate for monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO). Because we have recently reported that amine oxidase substrates promote glucose transport in rat and human adipocytes, the in vitro octopamine effects on lipolysis and glucose uptake were reassessed by using adipocytes from beta3-AR-deficient mice. The lipolytic effect and the counter-regulation of insulin action on glucose transport provoked by 0.1 to 1 mM octopamine or by 1 microM beta3-AR agonists found in control animals disappeared in adipocytes from beta3-AR-deficient mice. This revealed an insulin-like effect of octopamine on glucose uptake, which was dependent on its oxidation by MAO or SSAO, as was the case for tyramine and benzylamine, devoid of beta3-adrenergic agonism. Similarly, octopamine promoted glucose transport in human adipocytes and exhibited a weaker lipolytic stimulation than in rodent adipocytes. These findings indicate that, besides its lipolytic activity, octopamine exerts, at millimolar dose, dual effect on glucose transport in adipocytes: counteracting insulin action via beta3-AR activation and stimulating basal transport via its oxidation by MAO or SSAO.

Adipocytes↗

Targets of octopamine action in the lobster: cyclic nucleotide changes and physiological effects in hemolymph, heart and exoskeletal muscle.

We have examined three potential targets of octopamine action of the lobster--hemolymph, heart and exoskeletal muscle--and found that each tissue responds to the amine with increases in cyclic adenosine 3': 5'-monophosphate (cAMP) and changes in measurable physiological phenomena. A highly specific octopamine-stimulated increase in cAMP is observed in hemolymph, and this effect is probably due to the presence of a unique octopamine receptor on hematocytes. Pharmacological studies show that synephrine is a potent agonist of the hemolymph receptor for octopamine and that the alpha adrenergic receptor blockers phentolamine and dibenamine and the dopamine receptor blocker, chlorpromazine, are antagonists. Addition of octopamine to lobster hemolymph increases the rate of changes the nature of the clotting reaction. AMP levels in lobster heart are elevated by both octopamine and serotonin. Both amines also increase the rate and the amplitude of the heart beat. Octopamine, serotonin and dopamine all increase cAMP levels in lobster exoskeletal muscle preparations, and each amine causes changes in muscle tension and the strength of nerve evoked contractions. In none of the tissues studied have we been able to establish a direct relationship between amine-stimulated increases in cAMP levels and the physiological responses.

Animals↗

Effects of octopamine on GABA-ergic transmission in rats.

The behavioral effects of octopamine (50, 100 and 250 micrograms/rat ivc) and GABA-ergic drugs alone or in combination were studied in rats. Octopamine significantly increased locomotor activity in all doses tested. In rats pretreated with muscimol (0.5 mg/kg sc) or baclofen (2.5 mg/kg ip) octopamine did not produce hyperactivity. Octopamine in all doses did not affect bicuculline (3.5 mg/kg sc) -induced convulsions. Picrotoxin (0.4 mg/kg sc) inhibited the stimulatory action of octopamine but at the same time produced signs of toxicity. Biochemical studies showed that octopamine decreased the cerebral concentration of GABA and reduced activity of GAD in rats brain. Significant changes in concentrations of NA and DA in brain of rats pretreated with baclofen and octopamine were found.

Animals↗

Octopamine as a putative neurotransmitter.

Octopamine is a normally occurring amine in nervous tissues in many species of animals. In mammals, octopamine is formed from tyramine through beta-hydroxylation by DBH in the sympathetic nerves, and it is partially stored in nerve endings with a subcellular distribution similar to that of NE. It is capable of replacing NE in its storage sites, and it is released by sympathetic nerve stimulation. High concentrations are found in the crustacean central nerve cord. Specific octopamine-containing cells have been identified in Aplysia and other lower animals. On the basis of neurophysiological evidence, the existence of specific octopamine receptors in Aplysia has been postulated. In insects, octopamine produces specific biochemical responses such as increased synthesis of cyclic AMP and phosphorylase activation. The present evidence strongly suggests that octopamine may function as a neurotransmitter in lower animals. Although the physiological role of this amine has not been established in mammals, it appears likely that octopamine may function as a cotransmitter together with NE in the peripheral sympathetic nervous system.

Adenylyl Cyclases↗

Characterization of Drosophila tyramine beta-hydroxylase gene and isolation of mutant flies lacking octopamine.

Octopamine is likely to be an important neuroactive molecule in invertebrates. Here we report the molecular cloning of the Drosophila melanogaster gene, which encodes tyramine beta-hydroxylase (TBH), the enzyme that catalyzes the last step in octopamine biosynthesis. The deduced amino acid sequence of the encoded protein exhibits 39% identity to the evolutionarily related mammalian dopamine beta-hydroxylase enzyme. We generated a polyclonal antibody against the protein product of T beta h gene, and we demonstrate that the TBH expression pattern is remarkably similar to the previously described octopamine immunoreactivity in Drosophila. We further report the creation of null mutations at the T beta h locus, which result in complete absence of TBH protein and blockage of the octopamine biosynthesis. T beta h-null flies are octopamine-less but survive to adulthood. They are normal in external morphology, but the females are sterile, because although they mate, they retain fully developed eggs. Finally, we demonstrate that this defect in egg laying is associated with the octopamine deficit, because females that have retained eggs initiate egg laying when transferred onto octopamine-supplemented food.

Animals↗

Octopamine modulates the responses and presynaptic inhibition of proprioceptive sensory neurones in the locust Schistocerca gregaria

A multineuronal proprioceptor, the femoral chordotonal organ (feCO), monitors the position and movements of the tibia of an insect leg. Superfusing the locust metathoracic feCO with the neuromodulator octopamine, or the octopamine agonist synephrine, affects the position (tonic) component of the organ's response, but not the movement (phasic) component. Both octopamine and synephrine act with the same threshold (10(-6) mol l-1). Individual sensory neurones that respond tonically at flexed tibial angles show increased tonic spike activity following application of octopamine, but those that respond at extended angles do not. Tonic spiking of phaso-tonic flexion-sensitive neurones is enhanced but their phasic spiking is unaffected. Bath application of octopamine to the feCO increases the tonic component of presynaptic inhibition recorded in the sensory terminals, but not the phasic component. This inhibition should at least partially counteract the increased sensory spiking and reduce its effect on postsynaptic targets such as motor neurones. Furthermore, some phasic sensory neurones whose spiking is not affected by octopamine nevertheless show enhanced tonic synaptic inputs. The chordotonal organ is not known to be under direct efferent control, but its output is modified by octopamine acting on its sensory neurones to alter their responsiveness to mechanical stimuli and by presynaptic inhibition acting on their central branches. The effects of this neuromodulator acting peripherally on sensory neurones are therefore further complicated by indirect interactions between the sensory neurones within the central nervous system. Increases of sensory neurone spiking caused by neuromodulators may not necessarily lead to parallel increases in the responses of postsynaptic target neurones.

Journal Article↗

A chemical ionization gas chromatographic mass spectrometric assay for octopamine and tyramine in rat brain.

A method has been developed for the quantitation of the putative phenolamine neurotransmitter octopamine, and its precursor tyramine, in brain tissue. The procedure employs methane chemical ionization of the pentafluoropropionate derivatives of octopamine and tyramine together with the use of deuterated internal standards and selected ion monitoring. Deuterated analogues of octopamine and tyramine are added to brain homogenates in aqueous perchloric acid and ion exchange is used to isolate the brain amines. The method is capable of measuring 20 pg of octopamine and tyramine. The measured concentration (ng g-1 wet tissue) of octopamine and tyramine in rat brain was as follows: whole brain (less cerebellum) (0.6 and 2.2); hypothalamus (3.2 and tyramine value not statistically significant); striatum (0.5 and 11.8) and cortex (0.6 and 1.0). Administration of pargyline resulted in an increase (around ten-fold) in octopamine and tyramine concentration in all the above brain regions. In contrast alpha-methyltyrosine produced only a small increase (50%) in the concentration of tyramine in the striatum.

Animals↗

Pre- and postsynaptic effects of p-tyramine and p-octopamine in the prostatic portion of the rat vas deferens.

The effect of p-tyramine and p-octopamine on the twitch responses of the prostatic portion of the rat vas deferens to electrical stimulation (0.025 Hz) were compared with the effects of noradrenaline. In tissues with normal monoamine oxidase (MAO) activity, the three amines increased the height and duration of the twitch contractions. When MAO activity was inhibited by pargyline (10 mumol/l), p-tyramine and p-octopamine had mixed excitatory-inhibitory effects on the twitches, while noradrenaline had mostly excitatory effects along the whole range of concentrations assayed (0.158-15.8 mumol/l). Selective blockade of alpha 1- and alpha 2-adrenoceptors, by corynanthine and yohimbine, respectively, showed that the excitatory effect of the amines depended on the activation of alpha 1-adrenoceptor and that the inhibitory action was related to the activation of alpha 2-adrenoceptors. Pretreatment with reserpine (5 mg/kg, 24 h; 2.5 mg/kg, 2 h before the experiment) largely prevented the effects of p-tyramine and p-octopamine, but the amines still modified the twitch responses to field stimulation. The addition of corynanthine and yohimbine to the bathing fluid revealed a considerable activation of alpha 1-excitatory and alpha 2-inhibitory adrenoceptors. Cocaine (10 mumol/l) did not antagonize, but rather enhanced the inhibitory effects of p-tyramine and p-octopamine in tissues with normal contents of noradrenaline. Moreover, cocaine did not antagonize the inhibition caused by p-tyramine, and enhanced the inhibition induced by p-octopamine in the prostatic portion of the vasa deferentia from reserpine-pretreated animals. These results suggest that in this tissue, at least when MAO activity is inhibited, p-tyramine and p-octopamine behave similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗

Characterization of insect neuronal octopamine receptors (OA3 receptors).

Octopamine receptors in the nervous tissue of insects were investigated using a ligand-receptor assay with [3H]NC-5Z or [3H]octopamine as the radioligands. Both ligands recognized a homogeneous class of binding sites with the properties of an octopamine receptor. This receptor has been characterized pharmacologically. Both high-affinity agonists (e.g. NC 7, K1 = 0.3 nM) and antagonists (e.g. maroxepine, K1 = 1.02 nM) were investigated. The neuronal octopamine receptor belongs to a receptor class that can easily be distinguished from peripheral octopamine receptors. Initial investigations of the localization of octopamine receptors within the insect nervous tissue show the greatest receptor density in the optic lobes.

Animals↗

Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells.

Numerous synthetic agonists selectively stimulate beta3-adrenoceptors (ARs). The endogenous catecholamines, noradrenaline and adrenaline, however, stimulate all the beta-AR subtypes, and no selective physiological agonist for beta3-ARs has been described so far. The aim of this study was to investigate whether any naturally occurring amine can stimulate selectively beta3-ARs. Since activation of lipolysis is a well-known beta-adrenergic function, the efficacy and potency of various biogenic amines were compared with those of noradrenaline, isoprenaline, and beta3-AR agonists 4-(-{[2-hydroxy-(3-chlorophenyl)ethyl]-amino} propyl)phenoxyacetate (BRL 37,344) and (R,R)-5-(2-{[2-(3-chlorophenyl )-2-hydroxyethyl]-amino} propyl)-1,3-benzo-dioxole-2,2-dicarboxylate (CL 316,243) by testing their lipolytic action in white fat cells. Five mammalian species were studied: rat, hamster and dog, in which selective beta-AR agonists act as full lipolytic agents, and guinea-pigs and humans, in which beta3-AR agonists are less potent activators of lipolysis. Several biogenic amines were inefficient (e.g. dopamine, tyramine and beta-phenylethylamine) while others (synephrine, phenylethanolamine, epinine) were partially active in stimulating lipolysis in all species studied. Their actions were inhibited by all the beta-AR antagonists tested, including those selective for beta1- or beta2-ARs. Octopamine was the only amine fully stimulating lipolysis in rat, hamster and dog fat cells, while inefficient in guinea-pig or human fat cells, like the beta3-AR agonists. In rat white fat cells, beta-AR antagonists inhibited the lipolytic effect of octopamine with a relative order of potency very similar to that observed against CL 316,243. Competitive antagonism of octopamine effect resulted in the following apparent pA2 [-log(IC50), where IC50 is the antagonist concentration eliciting half-maximal inhibition] values: 7.77 (bupranolol), 6.48 [3-(2-ethyl-phenoxy)-1[(1 S)-1,2,3,4-tetrahydronaphth-1-ylaminol]-(2S)2-propanol oxalate, SR 59230A, a beta3-selective antagonist], 6.30[erythro-D,L-1(7-lethylindan-4-yloxy)-3-isopropylamino-+ ++butan-2-ol, ICI 118,551, a beta2-selective antagonist] and 4.71 [(+/-)-[2-(3-carbomyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1- methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]2-propanolmethane sulphonate, CGP 20712A, a beta1-selective antagonist]. Octopamine had other properties in common with beta3-AR agonists: stimulation of oxygen consumption in rat brown fat cells and very low affinity in displacing [3H]CGP 12,177 binding to [beta1- or beta2-ARs in dog and rat adipocyte membranes. In Chinese hamster ovary (CHO) cells expressing human beta3-ARs, octopamine inhibited [125I]ICYP binding with only twofold less affinity than noradrenaline while it exhibited an affinity around 200-fold lower than noradrenaline in CHO cells expressing human beta1- or beta2-ARs. These data suggest that, among the biogenic amines metabolically related to catecholamines, octopamine can be considered as the most selective for beta3-ARs.

Adipose Tissue↗

Octopamine modulates responsiveness to foraging-related stimuli in honey bees (Apis mellifera).

The biogenic amine neurochemical octopamine is involved in the onset of foraging behaviour in honey bees. We tested the hypothesis that octopamine influences honey bee behavioural development by modulating responsiveness to task-related stimuli. We examined the effect of octopamine treatment on responsiveness to brood pheromone (an activator of foraging) and to the presence of older bees in the colony (an inhibitor of foraging in young bees). Octopamine treatment increased responsiveness to brood pheromone and decreased responsiveness to social inhibition. These results identify octopamine both as an important source of variation in response thresholds and as a modulator of pheromonal communication in insect societies. We speculate that octopamine plays more than one role in the organisation of behavioural development indicating a very high level of integration between the neurochemical system and the generation of complex behaviour.

Aging↗

Aminergic neuron systems of lobsters: morphology and electrophysiology of octopamine-containing neurosecretory cells.

In the American lobster (Homarus americanus) the biogenic amines serotonin and octopamine appear to play important and opposite roles in the regulation of aggressive behavior, in the establishment and/or maintenance of dominant and subordinate behavioral states and in the modulation of the associated postural stances and escape responses. The octopamine-containing neurosecretory neurons in the thoracic regions of the lobster ventral nerve cord fall into two morphological subgroups, the root octopamine cells, a classical neurohemal group with release regions along second thoracic roots, and the claw octopamine cells, a group that selectively innervates the claws. Cells of both subgroups have additional sets of endings within neuropil regions of ganglia of the ventral nerve cord. Octopamine neurosecretory neurons generally are silent, but when spontaneously active or when activated, they show large overshooting action potentials with prominent after-hyperpolarizations. Autoinhibition after high-frequency firing, which is also seen in other crustacean neurosecretory cells, is readily apparent in these cells. The cells show no spontaneous synaptic activity, but appear to be excited by a unitary source. Stimulation of lateral or medial giant axons, which excite serotonergic cells yielded no response in octopaminergic neurosecretory cells and no evidence for direct interactions between pairs of octopamine neurons, or between the octopaminergic and the serotonergic sets of neurosecretory neurons was found.

Animals↗

The normal occurrence of octopamine in the central nervous system of the rat.

An enzymatic assay for octopamine capable of detecting 50 pg of amine was developed and used to study the distribution of octopamine in regions of the rat central nervous system. The presence of octopamine in the rat pineal organ was confirmed by mass spectrometry; Administration of a monoamine oxidase inhibitor and of tyramine led to increases in CNS octopamine levels while the administration of reserpine intraperitoneally or 6-hydroxydopamine intraventricularly led to decreases in octopamine levels. The results suggest that in the mammalian CNS octopamine is present in neural structures where it may be involved in synaptic function.

Animals↗

XAMI and DCDM, agonists at cAMP-associated octopamine receptors in cockroach nerve cord, produce centrally mediated antinociception in mice.

The ability of XAMI (2,3-xylylaminomethyl-2'-imidazoline), the most potent agonist of cAMP-associated octopamine-sensitive adenylate cyclase in cockroach (Periplaneta americana) nerve cord yet reported, and DCDM (N-demethylchlordimeform), a partial octopamine agonist in this preparation, to produce centrally mediated antinociception in mice was evaluated. The antinociception produced by these compounds was compared to that previously reported for p-octopamine, a phenylethylamine and endogenous mammalian hydroxyphenolic analog of norepinephrine. Consonant with the reported greater agonistic activity of XAMI on octopamine-sensitive adenylate cyclase, XAMI was more potent than p-octopamine by spinal or supraspinal administration in the abdominal constriction test (E50 = 0.013 micrograms i.t., 1.45 micrograms i.c.v.) and in the 48 degrees C hot-plate test (ED50 = 0.06 micrograms i.t., 0.4 micrograms i.c.v.), but was inactive in the tail-flick test (up to 4.0 micrograms i.c.v. or i.t.). Unlike p-octopamine, both XAMI and DCDM were active by peripheral routes of administration. DCDM was orally active in the mouse acetylcholine-induced abdominal constriction test (ED50 = 9.98 mg/kg p.o.) and was active via the s.c. route in this test (ED50 = 2.36 mg/kg), the 48 degrees C hot-plate test (ED50 = 5.40 mg/kg) and the tail-flick test (ED50 between 15 and 30 mg/kg). It appeared to be a full agonist against these endpoints. XAMI produced dose-related antinociception in the abdominal constriction test (ED50 = 0.10 mg/kg s.c.) and in the 48 degrees C hot-plate test (ED50 = 3.71 mg/kg p.o. and 0.46 mg/kg s.c.), where the antinociceptive response persisted for at least 60 min following subcutaneous or oral administration. Both compounds were less potent via peripheral routes than clonidine (as reference) in these tests. Mechanistically, XAMI-induced antinociception was antagonized by yohimbine and idazoxan, but not the opiate antagonist naloxone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗

Pharmacological characterization of octopamine-sensitive adenylate cyclase in the flight muscle of Locusta migratoria L.

Octopamine stimulates (20-30-fold) the adenylate cyclase activity in a broken cell preparation of locust flight muscle. This stimulation is mediated by one receptor with an apparent affinity of 3.3 X 10(-6) M. The hydroxyl group in the para position on phenylethanolamine was absolutely necessary to obtain an agonist whereas the meta hydroxyl group or the presence of a catechol almost suppressed the activity. Similar pharmacological profiles were obtained on other locust muscles, i.e. mandibular and extensor tibiae muscles. The affinities of a large series of agonists and antagonists for the octopamine receptor coupled with an adenylate cyclase were compared to those reported for octopamine 1, 2A and 2B receptors based on physiological studies in the locust extensor tibiae muscle. It appears that the octopamine receptor coupled with adenylate cyclase is likely to be identical with the octopamine 2A receptor mediating the increase in the amplitude of slow motoneuron twitch tension. The results of the pharmacological experiments are discussed, in particular concerning the possible relationship between the octopamine receptor and alpha 1- and alpha 2-adrenoceptors.

Adenylyl Cyclases↗

Interaction of formamidines with octopamine-sensitive adenylate cyclase receptor in the nerve cord of Periplaneta americana L.

Chlordimeform (CDM) and demethylchloridimeform (DCDM) mimic the action of octopamine in elevating adenylate cyclase activity in intact nerve cords of the American cockroach, Periplaneta americana. At a concentration of 1 x 10(-5)M, DCDM (13.5x increase within 20 minutes) is a more potent effector of the response than CDM (3x increase within 20 minutes), but both compounds show less efficacy than octopamine (23.5x increase within 15 minutes). DCDM also mimics the stimulatory effect of octopamine on adenylate cyclase activity in nerve cord homogenates whereas CDM has no demonstrable effect on this preparation. The octopamine- and DCDM-induced responses are competitively inhibited by phentolamine (1 x 10(-6)M) and cyproheptadine (1 x 10(-6)M) but not by propranolol (1 x 10(-6)M). DCDM and CDM inhibit the octopamine-induced activation of adenylate cyclase by 33% and 44% respectively. The results are discussed in light of the proposal that DCDM serves as a partial agonist and CDM as an antagonist of the octopamine receptor.

Adenylyl Cyclases↗