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Effects of medroxtprogesterone acetate (MPA) on adenylate cyclase activity in rat mammary tumours
419
Pharmacological Research, Vol. 22, Supplement 2,1990
EFFECTS OF MEDROXYPROGESTERONE ACETATE (MPA) ON ADENYLATE CYCLASE ACTIVITY IN RAT MAMMARY TUMOURS Racca S.O, ~ROZZI S.o, Conti G.o, Badino P.~ Giubertoni M.o, Squillario P. o, Paradisi L. and Di Carlo F.o o 2° Cattedra di Farmacologia e Dipartimento di Medicina e Oncologia Sperimentale, Universita di Torino, Italia In previous studies we observed that MPA is effective as an antitumoral drug in the dimethylbenzanthracene (DMBA)-induced rat mammary carcinoma model and that its antineoplasticoction is accompanied by a significant increase in tumoral cAMP levels, which is probably correlated with a stimulation of adenylate cyclase system (AC). In control animals the tumoral AC is not able to respond to stimulatory regulation of glucagon and epinephrine, while in MPA-treated rats the enzyme of regre~sing tumours regains the ability to respond to such hormonal stimulation. The aim of the present research was to establish theoomponent of the AC system (receptors, catalytic unit, G proteins) on which MPA actually acts. MPA (75mg/Y.g/die) was injected i.m. for 15 days in 50 Sprague-~awley female rats bearing DMBA induced mammary tumours. About 34% of tumours regressed after treatment (more than 75% regression). In these animals a significant increase of cAMP levels was observed as in previous studies. The AC activity of control and non responsive tumours was not changed by the addition of GTP6s, forskolin, cholera and pertussis toxin to the incubation system. On the contrary the enzyme activity of responsive tumours was stimulated by GTPt s addi t i on , This result suggests that MPA probably acts on GTP-dependent control of the AC activity.
1043---6618/90/22110419---01/$03.00/0
© 1990The Italian Pharmacological Society
Pharmacological Research, Vol. 22, Supplement 2,1990
EFFECTS OF MEDROXYPROGESTERONE ACETATE (MPA) ON ADENYLATE CYCLASE ACTIVITY IN RAT MAMMARY TUMOURS Racca S.O, ~ROZZI S.o, Conti G.o, Badino P.~ Giubertoni M.o, Squillario P. o, Paradisi L. and Di Carlo F.o o 2° Cattedra di Farmacologia e Dipartimento di Medicina e Oncologia Sperimentale, Universita di Torino, Italia In previous studies we observed that MPA is effective as an antitumoral drug in the dimethylbenzanthracene (DMBA)-induced rat mammary carcinoma model and that its antineoplasticoction is accompanied by a significant increase in tumoral cAMP levels, which is probably correlated with a stimulation of adenylate cyclase system (AC). In control animals the tumoral AC is not able to respond to stimulatory regulation of glucagon and epinephrine, while in MPA-treated rats the enzyme of regre~sing tumours regains the ability to respond to such hormonal stimulation. The aim of the present research was to establish theoomponent of the AC system (receptors, catalytic unit, G proteins) on which MPA actually acts. MPA (75mg/Y.g/die) was injected i.m. for 15 days in 50 Sprague-~awley female rats bearing DMBA induced mammary tumours. About 34% of tumours regressed after treatment (more than 75% regression). In these animals a significant increase of cAMP levels was observed as in previous studies. The AC activity of control and non responsive tumours was not changed by the addition of GTP6s, forskolin, cholera and pertussis toxin to the incubation system. On the contrary the enzyme activity of responsive tumours was stimulated by GTPt s addi t i on , This result suggests that MPA probably acts on GTP-dependent control of the AC activity.
1043---6618/90/22110419---01/$03.00/0
© 1990The Italian Pharmacological Society