Block of light responses of salamander rods by pertussis toxin and reversal by nicotinamide.
Transducin is the substrate for a pertussis toxin-catalyzed ADP-ribosylation in isolated retinal rod disk membranes [(1984) J. Biol. Chem. 259, 23-26]. The effects of the toxin on the light responses of intact dark-adapted rods were studied. Applied close to a rod outer segment in a retinal slice, pertussis toxin depolarized the rod by a few millivolts and produced a long-lasting depression of light responses, effects which depended on penetration of toxin into rods. Nicotinamide, an inhibitor of ADP-ribosylation, not only blocked the action of the toxin, but also reversed the effects once established. The action of nicotinamide itself on rods indicates the presence of endogenous ADP-ribosyltransferases which may constitute a control system modulating phototransduction. Inhibition of phospholipase C by neomycin had only transient effects indicating that the cGMP, rather than a phosphoinositide, pathway is primary in vertebrate phototransduction. Rapid reversal of pertussis toxin action suggests possible clinical applications of nicotinamide or congeners to the treatment of disease caused by ADP-ribosylating bacterial toxins.
Falk
G
G
Department of Physiology, University College London, England.
Shiells
R A
RA
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D008027:Light; D008565:Membrane Proteins / Q000378:metabolism; D009536:Niacinamide / Q000494:pharmacology*; D037342:Pertussis Toxin; D010775:Photic Stimulation; D010786:Photoreceptor Cells / Q000187:drug effects* / Q000378:metabolism; D015293:Transducin; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D014562:Caudata; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D008565:Membrane Proteins; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D009536:Niacinamide; D037342:Pertussis Toxin; D010738:Type C Phospholipases; D015293:Transducin; D006152:Cyclic GMP