Search

1. We designed and synthesized several novel cyclic MSH analogues and tested their affinities for cells expressing the MC1, MC3, MC4 and MC5 receptors. 2. One of the substances HS028 (cyclic [AcCys11, dichloro-D-phenylalanine14, Cys18, Asp-NH2(22)]-beta-MSH11-22) showed high affinity (Ki of 0.95nM) and high (80 fold) MC4 receptor selectivity over the MC3 receptor. HS028 thus shows both higher affinity and higher selectivity for the MC4 receptor compared to the earlier first described MC4 receptor selective substance HS014. 3. HS028 antagonised a alpha-MSH induced increase in cyclic AMP production in transfected cells expressing the MC3 and MC4 receptors, whereas it seemed to be a partial agonist for the MC1 and MC5 receptors. 4. Chronic intracerebroventricularly (i.c.v.) administration of HS028 by osmotic minipumps significantly increased both food intake and body weight in a dose dependent manner without tachyphylaxis for a period of 7 days. 5. This is the first report demonstrating that an MC4 receptor antagonist can increase food intake and body weight during chronic administration providing further evidence that the MC4 receptor is an important mediator of long term weight homeostasis.

DNA from different strains of Saccharomyces cerevisiae has been fractionated in preparative Ag+/Cs2-SO4 density gradients. The results show that there are real differences in amount of the nuclear satellite component, the gamma-DNA, from one strain to the other. The gamma-DNA forms a homogeneous dense band that contains all the rDNA, and the amount of gamma-DNA estimated from the gradients can be correlated to amount of rDNA derived from rRNA-DNA hybridizations. By various crossings and sporulations we have obtained diploid and haploid strains with gamma-DNA contents ranging from 7 to 20% of the nuclear DNA. During meiosis, the amount of gamma-DNA appears to segregate in a pattern that indicates unequal crossing over as a possible mechanism for differences in gamma-DNA contents.