Involvement of calcineurin in the signal transduction of PBAN in the silkworm, Bombyx mori (Lepidoptera).
In several moth species sex pheromone production in the pheromone gland is regulated by a neurohormone, pheromone biosynthesis activating neuropeptide (PBAN). In Bombyx mori it is suggested that PBAN, after binding to the cell-surface receptor, primarily activates a plasma membrane receptor-activated Ca2+ channel to increase cytosolic levels of Ca2+, and Ca2+/calmodulin complex directly or indirectly activates a phosphoprotein phosphatase, which in turn elicits activation of acyl CoA reductase (the key enzyme under PBAN control) through dephosphorylation, resulting in pheromone (bombykol) production. The effect of cyclosporin A (CsA) and FK 506, specific inhibitors of calcineurin (phosphoprotein phosphatase 2B) was studied on the sex pheromone production, in B. mori. The in vitro experiments showed that both chemicals exerted a dose-dependent inhibitory action when they were co-incubated with TKYFSPRL amide (Hez-PBAN fragment peptide). Practically, no difference was detected between the two chemicals in the tested doses (0.025-1250 microM). When effects of CsA or FK 506 were studied on cell-free production of bombykol by using microsomal fraction no inhibition was detected. Since microsomal fraction contains the acyl CoA synthetase, the rate-limiting acyl CoA reductase and the precursor, bombykol is produced if supplied with CoA, ATP and NADPH. Thus, the inhibitory action of CsA and FK506 under in vitro conditions should occur before the step of acyl group reduction and the effect is likely to be attributable to the inhibition of calcineurin in the signal transduction cascade mechanism of PBAN, in B. mori. The existence of calcineurin in the pheromone gland by using Western blot analysis is also demonstrated.
Fónagy
A
A
Plant Protection Institute of the Hungarian Academy of Sciences, Budapest, Hungary. h7191fon@ella.hu
Yokoyama
N
N
Ozawa
R
R
Okano
K
K
Tatsuki
S
S
Maeda
S
S
Matsumoto
S
S
D000818:Animals; D015153:Blotting, Western; D012831:Bombyx / Q000378:metabolism*; D019703:Calcineurin / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D002474:Cell-Free System / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005233:Fatty Alcohols / Q000037:antagonists & inhibitors; D005260:Female; D066298:In Vitro Techniques; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008148:Lovastatin / Q000031:analogs & derivatives / Q000494:pharmacology; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012724:Sex Attractants / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D016559:Tacrolimus / Q000494:pharmacology
D065095:Calcineurin Inhibitors; D005233:Fatty Alcohols; D019476:Insect Proteins; D009479:Neuropeptides; D012724:Sex Attractants; C079709:pheromone biosynthesis activating neuropeptide, Helicoverpa zea; C012258:mevastatin; C006787:bombykol; D016572:Cyclosporine; D008148:Lovastatin; D019703:Calcineurin; D016559:Tacrolimus