M-Octopamine

The addition reaction of carbon-11 labelled cyanide ion to the bisulphite addition adduct of an aldehyde has been extended to prepare carbon-11 labelled amines. Maeda and coworkers prepared both p- and m-octopamine [2-(p-and m-hydroxyphenyl)-2-hydroxyethyl-amine] from the corresponding benzaldehyde by reducing the cyanohydrin formed in the reaction between the appropriate benzaldehyde and cyanide ion both under enzymatic conditions and by the basic modification of the Bucherer-Strecker synthesis, with borane-THF. The synthesis of / -octopamine is presented in equation 64. 

Fig. 3. GC-MS selected ion-monitoring trace of pHj] and [ Hg] p-octopamine (as their DTFMB-TMS derivatives) from 50 DUM cells incubated with pHg] p-tyramme (A) Detection of endogenous p-octopamine (mass-to-charge ration 537) (B,C) Deu-terated pHg] p-octopamine (mass-to-charge ratio 542) and pHgjp-octopamine (mass-to-charge ration 543), respectively. These deuterated products must have been synthesized by the DUM cells from [ Hg] p-tyramine, because they are not present m the controls. Int. Std. Internal stan d (PH3] m-octopamine) added at the time of derivatization to allow quantification of amines recovered. The y-axis of the figine represents instrument response in arbitrary units. M/Z Mass-to-charge ratio for the particular 10ns being monitored, which in each case corresponds to the molecular weights of the derivatives of the species present.

Tyramine is produced by decarboxylation of tyrosine and is present in the CNS in higher (threefold) concentrations than m-tyramine, the hydroxylated derivative of phenylethylamine. In the periphery / -tyramine is easily hydroxylated to octopamine, which has some direct effects on ai adrenoceptors, unlike tyramine which functions by releasing NA. When tested on central neurons tyramine always produces the same effects as NA but they are slower and less marked, implying an indirect action. By contrast octopamine often produces the opposite effect to NA and it is probable that octopamine may have a functional role in the invertebrate CNS where it is found in higher concentrations (5pg/g) than in the mammalian brain (0.5ng/g). Neither tyramine nor octopamine have distinct behavioural effects, unlike phenylethylamine,... 

Hammer M. and Menzel R. (1998) Multiple sites of associative odor learning as revealed by local brain microinjections of octopamine in honeybees. Learn. Mem. 5, 146-156. 

Millard, B. J., Tippett, R. A., Couch, M. W., and Williams, C. M. (1977). Evidence for the lack of a carrier effect in the solvent extraction and determination of octopamine by gas chromatography-mass spectrometry. Biomed. Mass Spectrom. 4, 381-384. 

The excretion of amines is unusual in animals. Amines are highly toxic and one method employed by vertebrates to detoxify them is via monoamine oxidase, an enzyme which has been detected in H. diminuta (569). Amines can arise from the decarboxylation of the appropriate amino acid, e.g. glycine and alanine can give rise to methylamine and ethylamine, respectively. Another possible source of amines may be the reduction of azo or nitro compounds (39) and azo- and nitro-reductase activity has been reported from M. expansa (180, 181). Furthermore, the physiologically active amines octopamine, dopamine, adrenalin and serotonin (5-hydroxytryptamine) have been demonstrated in cestodes (283, 296, 435, 681, 682, 758, 859), where they probably function predominantly as neurotransmitters (see Chapter 2). 

Vehicle-injected flies exhibited a mildly elevated M.A.T. and a moderate meal size concomitantly, there was a decline in brain octopamine content but no change in brain dopamine levels (Table I). Reserpine treated flies exhibited a 10-fold rise in threshold relative to the vehicle-injected controls and a large increase in meal size. These flies were hyperphagic in that they consumed their own body weight in 1 M sucrose, more than double that of the untreated controls and 60 percent higher than the solvent controls. Brain levels of octopamine in the group injected with reserpine were significantly depleted relative to both untreated and solvent controls. 

Dudai, Y., Buxbaum, J., Corfas, G., and Ofarim, M., Formamidines interact with Drosophila octopamine receptors, alter the flies behavior, and reduce their learning ability, /. Comp. Physiol., 161 A, 739,1987. 

Hollingworth, R.M. and Murdock, L.L., Formamidine pesticides Octopamine-like actions in a firefly, Science, 208, 74,1980. 

Schwaerzel M, Monastirioti M, Scholz H, Friggi-Grelin F, Birman S, Heisenberg M (2003) Dopamine and octopamine differentiate between aversive and appetitive olfactory memories in Drosophila. J Neurosci 23 10495-10502... 

Jordan, R., Midgeley, J. M., Thonoor, C. M., Williams, C. M. Beta-adrenergic activities of octopamine and synephrine stereoisomers on guinea-pig atria and trachea. J. Pharm. Pharmacol. 1987, 39, 752-754. 

Hirashima, A., Kuwano, E. and Eto, M. (2003) Comparative receptor surface analysis of octopaminergic antagonists for the locust neuronal octopamine receptor. Comp. Biol. Chem., 27, 531-540. 

The rate of removal of -octopamine and N-acetyl OA was determined by injecting 5 yl of a solution containing 26 nmoles of the compound in cockroach physiological saline (16) (CPS) into the insect haemocoel and withdrawing 5 yl aliquots of haemolymph at various times after the initial injection Procedures for injection and haemolymph collection have been described previously (17) Each haemolymph sample was transferred immediately to a 1 5 ml polypropylene tube containing 370 yl 0 3 mM EDTA in 0.1 M perchloric acid and vortexed. Following centrifugation at 40,000 g for 30 min, a 5 yl aliquot of the supernatant was injected directly onto the HPLC column for analysis ... 

Figure 1. Chromatograms of -octopamine (OA) and N-acetyl -octopamine (N-acOA) obtained from standards (2ng OA and lng N-acOA) and a whole gut preparation incubated for 20 minutes in medium containing 5x10 M OA. (Chromatographic conditions as described in text.)...

Livingstone M, Harris-Warrick R, Kravitz EA (1980) Serotonin and octopamine produce opposite postures in lobsters. Science 208 76-79... 

The locust CNS contains approx 100 DUM neurons, distributed dorsomedially in the ganglia of the ventral nerve cord. These neurons contain and release p-octopamine (10). It is possible, therefore, to remove and maintain m vitro an approximately homogeneous population of DUM cell bodies to monitor the biosynthesis of p-octopamine (Fig. 2). Because of the stereotyped location and lai ge size of these cells, physiological confirmation of their identity prior to removal is unnecessary... 

Baines, R. A., Zhou, P, Midgley, J. M., Bacon, J. P., and Watson, D. G. (1996) p-Tyramine is a precursor for both p-octopamine and dopamine in the insect nervous system determination by GC/MS of deuterium incorporation. J. Neurochem, submitted for publication. 

Dopamine was produced by incubating liver microsomes of rabbits with p- and m-tyramine, noradrenaline, and normetanephrine by incubation with w-octopamine, and adrenaline by incubation with p- and w-methyloctop-amine/" The injection of labelled tyramine as well as of labelled octopamine in the intact animal (rat) caused the appearance of labelled noradrenaline and normetanephrine in the urine/ As tyramine is also hydroxylated to octopamine, it is possible that the production of noradrenaline from tyramine not only takes place via its conversion to dopamine, but also via its conversion to octopamine. The possibility that octopamine is produced by the hydroxylation of tyrosine to hydroxyphenylserine with ensuing decarboxylation is under discussion. The production of noradrenaline from 3,4-dihydroxyphenylserine, 192-201) amino-acid so far not discovered in the mammal could be demonstrated both in organ extracts and in intact animals. Finally, a transamination of 3-hydroxy- or 3,4-dihydroxyphenylpyruvate to the corresponding amino-acids (m-tyrosin, dopa), and their decarboxylation to m-tyramine and dopamine was observed in intact animals (cats). For the time being it is impossible to determine the importance of the means of formation of catecholamines which have been referred to here. Of the above-mentioned precursor substances, p- and m-tyramine,( octopamine, ... 

Tyramine is oxidized to octopamine by dopamine-jS hydroxylase causing hydroxylation of the carbon atom of its side chain. Octopamine is converted to / -hydroxymandelic acid either directly or after being methylated to AT-methyloctopamine. The introduction of an OH group in the meta or para position in the nucleus of / - and m-tyramine respectively leads in vitro to the production of dopamine it is not known if... 

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