PubMed · 2554544
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R D Burgoyne. 1989. Small GTP-binding proteins.. https://doi.org/10.1016/0968-0004(89)90281-8
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Until recently, the therapeutic effects of furocoumarins and furochromones plus UV-A light were thought to be due to their ability to form photoadducts with DNA in the cell nuclei; now it appears that membrane effector systems may be involved as targets. Here we show that in HeLa cells khellin at 1 and 5 microM final concentration, in combination with UV-A light, inhibits NaF-stimulated adenylyl cyclase activity and Pertussis Toxin (PT)-catalyzed ADP-ribosylation of alpha-subunits of inhibitory guanine nucleotide regulatory proteins (Gi) and increases GTPase activity. In the same experimental conditions, 8-methoxypsoralen (8-MOP), either alone or plus UV-A, does not affect adenylyl cyclase and GTPase activities. Our results suggest that in HeLa cells, through an interaction with a receptor and the mediation of Gi proteins, the adenylyl cyclase system is a target for khellin but not for 8-MOP.
Developmental changes in the responses of rat ventral prostate to isoproterenol (IPR) and forskolin (F) were studied in relation to the function of beta-adrenoceptor-adenylate cyclase system. The response of adenylate cyclase in the tissues to IPR at 10(-7)M and above was steadily enhanced after birth and reached a maximum at 12 weeks, followed by a decrease with age. In contrast, the response of the enzyme to F at 10(-7)M and above was highest at 2 weeks, but thereafter decreased. The changes in the response of the enzyme to IPR coincided with changes in the beta-adrenoceptor density and the binding ability of GTP binding proteins (G proteins) to GTP. The ADP-ribosylation of inhibitory G proteins (Gi proteins) catalyzed by pertussis toxin (IAP) decreased 70% in the tissues from 4 to 8 weeks, and then maintained this level. On the other hand, the ADP-ribosylation of stimulatory G proteins (Gs proteins) catalyzed by cholera toxin (CT) increased only 20% in the tissues from 2 to 4 weeks. Thus, the ratio of ADP-ribosylation of Gs to that of Gi significantly increased from 4 weeks, reaching a maximum at 12 weeks, but thereafter decreased gradually with age. These changes paralleled those in the function of G proteins and the response of the enzyme to IPR. It is suggested that the rapid and marked decrease in apparent level of Gi proteins in the rat ventral prostate after 4 weeks may have a key role in controlling the function of the beta-adrenoceptor-adenylate cyclase system in the tissues.
Cyclic ADP-ribose (cADPR) is a potent mediator of Ca2+ mobilization from intracellular stores in sea urchin eggs. However, the regulation of the cADPR-induced Ca2+ release system is not yet fully elucidated. We now report that spermine and related polyamines, in physiological concentrations, were able to inhibit the Ca2+ release induced by cADPR in sea urchin egg homogenate bioassays, as measured using the Ca2+ indicator fluo 3, but had no effect on the Ca2+ release induced by D-myo-inositol 1,4,5-trisphosphate (IP3) or by nicotinate adenine dinucleotide phosphate (NAADP). Spermine was a more potent inhibitor of the cADPR-induced Ca2+ release than spermidine and putrescine. Spermine inhibited not only the release induced by cADPR but also the Ca2+ release induced by caffeine and ryanodine. Finally, pretreatment of the sea urchin egg homogenates with caffeine or Sr2+ and Ca2+ prevented the inhibitory effect of spermine on cADPR-induced Ca2+ release. We propose that polyamines, which are present in millimolar concentrations in fertilized eggs, are specific inhibitors of the ryanodine channel and perhaps may serve as endogenous regulators of the cADPR-induced Ca2+ release system.