Inhibition of adenosine 3',5'-cyclic monophosphate phosphodiesterase by colchicine: implications for glucagon and corticosteroid secretion.
In the study reported, colchicine, often regarded as a specific inhibitor of microtubular function, was shown to exert a concentration-dependent inhibition of the low Km cyclic AMP phosphodiesterases of the pancreatic islet, adrenal cortex and various other tissues of the rat. The results indicated that colchicine is only slightly less active as an inhibitor of the enzyme than theophylline on a molar basis and kinetic analysis revealed that both inhibitors acted competitively in the case of the liver enzyme. Our results show that the inhibitory effect of colchicine upon cyclic AMP phosphodiesterase is a general property of the alkaloid at concentrations of 5 x 10(-5)M and above in both endocrine and non-endocrine tissues. Thus, results obtained employing colchicine at concentrations significantly greater than those which are known to lead to microtubular disaggregation must be viewed with great caution if incorrect implication of microtubular participation in biological processes is to be avoided. For example, we propose that the previously reported paradoxical stimulatory effects of colchicine on the secretion of glucagon from the rat pancreatic islet and on steroidogenesis in the rat adrenal may be due to cyclic AMP accumulation consequent upon phosphodiesterase inhibition in these endocrine tissues and not to microtubular disaggregation as has hitherto been assumed.
Ewart
R
R
Department of Medicine, University of Louisville School of Medicine, Kentucky.
Bradford
M
M
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000302:Adrenal Cortex / Q000201:enzymology; D000305:Adrenal Cortex Hormones / Q000378:metabolism; D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000201:enzymology; D007672:Kidney Cortex / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D010903:Pituitary Gland, Anterior / Q000201:enzymology; D051381:Rats; D012636:Secretory Rate / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D005934:Glucagon; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D003078:Colchicine