1 The kidney bean lectin, phytohaemagglutinin (PHA), induced a marked atrophy of skeletal muscle which was evident from the changes in tissue composition (protein, RNA, DNA and polyamine content) and from the reduction in weight and protein synthesis of hind leg muscles of rats fed on kidney bean-diets for four days. The P-adrenoceptor agonist, clenbuterol, induced skeletal muscle hypertrophy by transiently stimulating protein synthesis. As a consequence, the muscle loss caused by a short exposure to PHA was, in part, ameliorated by clenbuterol treatment. 2 Cardiac muscle was affected to a lesser extent than skeletal muscle by both clenbuterol and the lectin. However, there was evidence that protein synthesis in heart was reduced by PHA. 3 PHA had opposite effects on the gut, the lectin-induced hyperplasia of the jejunum was accompanied by a large increase in protein synthesis. Clenbuterol alone had no effect on the jejunum whereas a combination of PHA and clenbuterol appeared to exacerbate the effect of the lectin on gut. 4 Both the lectin-induced gut growth and the hypertrophy of skeletal muscle caused by clenbuterol were preceded by the accumulation of polyamines in the respective tissues. Of particular note was the observation that a significant increase in the proportion of the intraperitoneally injected '4C-labelled spermidine or putrescine taken up by the growing tissues could be detected by the second day. Therefore, the measurement of uptake of labelled polyamines may be used as a sensitive indicator of early alterations in tissue metabolism. Keywords: Clenbuterol; phytohaemagglutinin (PHA); protein synthesis; small intestine; skeletal muscle; heart; polyamines; growth; atrophy
IntroductionThe lectin component of raw kidney bean, the phytohaemagglutinin (PHA) is a potent growth factor for the rat small intestine and induces extensive hyperplastic and hypertrophic growth of the tissue (Oliveira et al., 1988;Pusztai et al., 1988 (Janne et al., 1978), although their precise role(s) and mode of action remain unknown. PHAinduced gut growth is preceded by polyamine accumulation in the tissue (Pusztai et al., 1989), not as the result of increased de novo synthesis of polyamines in situ, but by stimulation of polyamine uptake from the circulation (Bardocz et al., 1990a). Thus, the uptake of putrescine through the basolateral membrane increased within the first hour of lectin exposure. However, the effect wore off quickly, lasting for 24 h only (Bardocz et al., 1990b). In contrast, the stimulation of spermidine uptake from the circulation was not immediate but remained elevated and was stimulated liver;'." Macmillan Press Ltd, 1992 EFFECTS OF CLENBUTEROL PLUS PHA ON RAT TISSUES 477 further for as long as PHA was present in the bowel (Bardocz et al., 1990b).The present study was undertaken to establish firstly whether accumulation of polyamines occurs during clenbuterol-induced muscle hypertrophy and whether clenbuterol affects the uptake of polyamines from the circulation by skeletal muscle. Since PHA and ...