Dietary polyamines promote the growth of azoxymethane-induced aberrant crypt foci in rat colon

We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose- dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.      

Effect of morphine on the cAMP level of lymphocytes

A study was made of the effect of morphine on the cAMP level in peripheral blood lymphocytes in tobacco smoking and non-smoking donors. Morphine was shown to produce the naloxone-removable activation of adenylate cyclase, the relationship between enzymatic activity and opiate concentration in the medium being complex in nature. In tobacco smoking donors, the maximal effect on cAMP was produced by morphine at concentrations that were one order of magnitude higher than those in non-smoking ones. On the basis of the data obtained the assumptions are made (1) about the presence on the lymphocytes of opiate receptors whose action mode is associated with adenylate cyclase control, and (2) about the development during tobacco smoking of morphine tolerance at the level of opiate-dependent adenylate cyclase of lymphocytes.     

Importance of opiate receptor ligands in regulating lymphocyte proliferative activity

Effects of morphine (10(-12)-10(-6) M), metenkephalin (10(-12)-10(-6) M), beta-endorphin (10(-12)-10(-6) M), dalargin--synthetic analogue of leu-enkephalin (10(-12)-10(-7) M) and naloxone (10(-8)-10(-6) M) on lymphocytes of the human peripheral blood stimulated by polyclonal mitogens were studied. It was shown that morphine (10(-8)-10(-6) M) and dalargin (10(-12)-10(-7) M) inhibited the lymphocyte proliferative activity induced by optimal doses of phytohemagglutinin; effects of morphine and dalargin were blocked by naloxone. It was also found that beta-endorphin (10(-11)-10(9) M) inhibited the proliferative activity of lymphocytes stimulated by pokeweed mitogen; naloxone failed to block beta-endorphin effect.