Interaction of formamidines with octopamine‐, dopamine‐and 5‐hydroxytryptamine‐sensitive adenylate cyclase in the nerve cord of Periplaneta americana

Abstract

The interaction of chlordimeform, N'-demethylchlordimeform [N2-(4-chloro-o-toly1)-N'-methylformamidine], BTS-27271 (N'-methyl-N2-(2,4-xylyl)formamidine, the 2,4-xylyl analogue of N'-demethylformamidine], and amitraz with octopamine-, dopamine-, and 5-hydroxytryptamine-mediated enhancement of cyclic-AMP production was investigated in nerve cord homogenates of the American cockroach Peripfunetu umericuna. N'-Demethylchlordimeform, BTS-27271 and amitraz simulated the actions of the monoamines in enhancing cyclic-AMP production, whereas chlordimeform showed no such agonism. Additivity studies indicated that these formamidine derivatives were interacting with dopamine-and 5hydroxytryptamine-sensitive sites, in addition to their known interaction with octopamine-sensitive adenylate cyclase. N'-Demethylchlordimeform (Ki= 0 . 2~~) and amitraz ( K i = 0 . 5 p~) inhibited the dopamine-mediated response, but only N'-demethylchlordimeform ( K i = 2 p~) effected appreciable inhibition of the octopamine-response. Pharmacological characterisation of the formamidineinduced elevation of cyclic-AMP production indicated that the agonistic effects of formamidines are expressed primarily through the octopamine-sensitive adenylate cyclase, rather than the dopamine-or 5-hydroxytryptamine-sensitive sites. The results are discussed in the light of the proposal that the behavioural changes, associated with formamidine poisoning, reflect the cumulative effects of octopamine-agonism, and antagonism of the dopamine-and 5-hydroxytryptaminemediated processes.

Pharmacology of octopamine‐, dopamine‐, and 5‐hydroxytryptamine‐stimulated cyclic amp accumulation in the corpus cardiacum of the american cockroach, Periplaneta americana L

“…Comparison with other studies of 5-hydroxytryptamine pharmacology in insects is difficult because of the limited number of compounds used. The 5-hydroxytryptamine-sensitive adenylate cyclase of cockroach nerve cord [16,34] and CC ( Fig. 1) and that present in the ventral nerve cord of Manduca sexta [35] have a K, of approximately 1 pM, similar to that of many vertebrate 5-hydroxytryptamine receptors [36].…”

Calcium involvement in mediating the action of octopamine and hypertrehalosemic peptides on insect haemocytes

“…IP3 causes release of calcium from intracellular pools [16] and, either directly or indirectly, elicits the opening of 'calcium gates' in the plasma membrane [17]. It is possible that the octopamine-receptor, which is involved in the increased cytosolic calcium concentrations observed in the present study, may also be coupled to phospholipase C. Mianserin, which is an inhibitor of 5-hydroxytryptamine-and histamine-receptors in vertebrate systems, is a potent inhibitor of octopaminemediated activation of adenylate cyclase in insects [2,18]. Mianserin also blocks the octopamineinduced elevation of cytosolic calcium levels in cultured haemocytes (figs 2 and 3) but does not affect the actions of HT-I, HT-II or A23187 in this regard.…”

“…Mianserin, the antagonist of octopaminemediated elevation of cyclic AMP in insects, inhibits the octopamine effect on intracellular 4. DISCUSSION Octopamine-sensitive receptors that are coupled to adenylate cyclase complexes have been demonstrated in several insect tissues and species [2][3][4][5][6][7]. Octopamine increases cyclic AMP production in cultured haemocytes of M. disstria [14] and, in addition, elicits rapid elevation of cytosolic However, the magnitude of the increase in cytosolic calcium levels is dependent upon the concentration of extracellular calcium (table 1), therefore, the mechanism may also involve stimulation of calcium entry from the extracellular environment.…”

“…Extensive studies on a variety of tissues from several insect species indicate that some actions of octopamme are mediaed through the interaction of octopamine with a specific receptor that is coupled to an adenylate cyclase complex and consequent elevation of intracellular concentrations of cyclic AMP [2][3][4][5][6][7]. At least two classes of octopamine receptor have been recognised pharmacologically and it is likely that, as is the case with vertebrate catecholamine, there are other mechanisms by which octopamine action may be mediated.…”

The crystal structure of 2-(4-bromophenyl)-4-(2-fluoroethyl)-5,6-dihydro-4H-1,3,4-oxadiazine hydrochloride, an octopaminergic insecticide/miticide

“…Compounds that stimulate octopaminergic systems in insects and mites have the potential to cause physiological, behavioral, and lethal effects that often are highly compatible with integrated pest management (IPM) systems. The octopamine receptor has been recognized as a useful target since the discovery of the insecticidal and miticidal properties of formamidines, which function as octopamine agonists by stimulating cyclic adenosine monophosphate (cyclic AMP) (8)(9)(10). Two formamidines, chlordimeform 2 and amitraz 3, are commercial pesticides (1 1).…”