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Horm Metab Res 1978; 10(5): 415-419
DOI: 10.1055/s-0028-1093404
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© Georg Thieme Verlag KG Stuttgart · New York

Cyclic AMP Inhibition of Mammary Gland Lactose Synthesis: Specificity and Potentiation by 1-Methyl-3-Isobutylxanthine[*]

R. F. Loizzi
  • Department of Physiology, School of Basic Medical Sciences, University of Illinois College of Medicine, Chicago, Illinois, U.S.A.
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Publication Date:
23 December 2008 (online)

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Abstract

When slices of lactating guinea pig mammary gland were incubated with 10-4 M 5'AMP, ATP, cAMP and cGMP, only the cAMP significantly inhibited lactose synthesis (26%). The drug 1-methyl-3-isobutylxanthine (MIX), a highly specific and potent inhibitor of cyclic AMP phosphodiesterase, inhibited synthesis in a dose-response fashion from 10-5 to 10-3 M with 50% inhibition at approximately 10-4 M. Theophylline was approximately one-third more potent than MIX at 10-4 but equipotent at 10-3 M. Potentiation of dibutyryl cAMP (DBcAMP) by MIX, due to weak (24%) DBcAMP inhibition, was observed only with a low MIX concentration (10-5) combined with DBcAMP preincubation (0°C, 30 min) resulting in a 33% inhibition by the two drugs together vs. 17% by MIX (p<0.05). Inhibition was also observed with 8-p-chlorophenylthio-cAMP (CIPheS-cAMP), an analogue reportedly 100 × as potent as cAMP. CIPheS-cAMP produced the same 30-40% maximum inhibition as DBcAMP but with 1/100 the dose (10-7 M). Cholera toxin in the range 0.001 to 10 µg/ml had no effect on release of lactose by gland slices over a 2 1/2-hr period or on lactose synthesis. The experiments demonstrate that cAMP inhibition of mammary gland lactose synthesis is weak but strongly specific and it is potentiated by phosphodiesterase inhibitors but the additivity is easily masked due to the potency of MIX. Finally, lactating alveolar cells may be missing a receptor for cholera toxin or a transducer linking the receptor to adenylate cyclase.

Key words

Cyclic AMP - Mammary Gland - Lactose - MIX - Guinea Pig

1 This work was supported in part by USPHS Grants GRSG 603 and HD 09035. Preliminary results were presented at the 61st Meeting of the Federation of American Societies for Experimental Biology and Medicine in April, 1977, Chicago, Illinois, U.S.A.

1 This work was supported in part by USPHS Grants GRSG 603 and HD 09035. Preliminary results were presented at the 61st Meeting of the Federation of American Societies for Experimental Biology and Medicine in April, 1977, Chicago, Illinois, U.S.A.

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