Receptors, octopamine

The target sites within the nervous system of insects known at present are very restricted. They consist of the sodium channel, the components of the nicotinic cholinergic synapse and the y-aminobutyric acid (GABA) and octopamine receptors. Benson4 (1991) lists potential target sites within the insect neuronal and muscular system. These are shown in Table 3.1. 

Rafaeli A., Gileadi C. and Hirashima A. (1999) Identification of novel synthetic octopamine receptor agonists which inhibit moth sex pheromone production. Pestic. Biochem. Physiol. 65, 194-204. 

Chen, A.C., He, H., and Davey, R.B., Mutations in a putative octopamine receptor gene in amitraz-resistant cattle ticks, Vet. Parasitol., 148, 379, 2007. 

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. 

More recently, Chen et al. (2007) found two amino acid substitutions (T8P, L22S) in a putative octopamine receptor in amitraz-resistant cattle ticks. Thus, point mutations may play a role in resistance to formamidine pesticides in ticks. 

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. 

Compounds that alter insect behavior in other ways may also be useful e.g. chemicals that increase insect locomotor activity should enhance the uptake of pesticides from treated surfaces. Such compounds are already known among the formamidines insecticides and their relatives that stimulate octopamine receptors (12), and further research in this area of pest biochemistry could reveal other locomotor stimulators such as phosphodiesterase inhibitors. A... 

Extensive pharmacological investigations of octopamine receptors have been reported for locust skeletal muscle (87), firefly lantern (8j2, 89), tobacco hornworm central nervous system (88,89),... 

One of the general features of octopamine receptors appears to be their susceptibility to vertebrate -adrenergic receptor antagonists, and their insensitivity to -adrenergic antagonists. 

Interest in octopamine receptors has grown with the discovery that a novel group of pesticides, the formamidines, are octopamine agonists (95). Thus chlordimeform (CDM) or demethylchlordimeform (DCDM) are able to activate octopamine receptors in firefly lantern (95,96), tobacco hornworm central nervous system (88), locust skeletal muscle (97), locust oviduct muscle (91,), locust corpora cardiaca (98), locust fat body (99). and cockroach haemocytes (39). 

In 1979, we discovered that the light organ of the firefly has a virtually pure population of octopamine receptors, with no evidence of adenylate cyclases activated by other hormones (16) Indeed, the octopamine-sensitive adenylate cyclase in this tissue is more active than any other hormone-activated adenylate cyclase yet reported in the animal kingdom This allowed us to carry out the first detailed pharmacological characterization of an octopamine-sensitive adenylate cyclase in the absence of other amine receptors (16-18) It also allowed us, more recently, to characterize a new chemical class of octopamine receptor agonists, the phenylimino-imidazolidines (see below) (19-21) ... 

Through use of the virtually pure octopaminergic firefly system, we have now acquired some idea of the structure-activity requirements for activation of this octopamine-sensitive adenylate cyclase. Furthermore, by quantitating the octopamine agonist potencies of a large series of chemically-related derivatives, we are now in an excellent position to characterize octopamine receptors in other, less homogenous tissues as well as in other insect species. 

These results further support the hypothesis that potent synthetic agonists of octopamine-sensitive adenylate cyclase should be useful as selective pesticides. The results also suggest that if compounds could be developed which were potent against the octopamine-sensitive adenylate cyclases present in a wide variety of insect species, they should, similarly, have a wide spectrum of insecticidal activity. However, in order to develop such compounds, much more needs to be known about a) the molecular pharmacology of octopamine receptors and b) the interspecies differences which seem to exist in the characteristics of such receptors. In other words, we need to know if there exist single or multiple octopamine receptor subtypes which interact with adenylate cyclase, and if multiple, how these subtypes vary among different species. 

One possibility would be to use labeled octopamine, itself, and to perform ligand binding studies of the type which are frequently used in mammalian neurotransmitter receptor research. The problem with this approach is that octopamine binds, to a large extent, to octopamine receptors other than those associated with adenylate cyclase. Thi is shown by the fact that the binding affinity reported for H-octopamine in insect nerve tissue is in the low... 

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