Oxytocin releases atrial natriuretic peptide by combining with oxytocin receptors in the heart

Previous studies indicated that the central nervous system induces release of the cardiac hormone atrial natriuretic peptide (ANP) by release of oxytocin from the neurohypophysis. The presence of specific transcripts for the oxytocin receptor was demonstrated in all chambers of the heart by amplification of cDNA by the PCR using specific oligonucleotide primers. Oxytocin receptor mRNA content in the heart is 10 times lower than in the uterus of female rats. Oxytocin receptor transcripts were demonstrated by in situ hybridization in atrial and ventricular sections and confirmed by competitive binding assay using frozen heart sections. Perfusion of female rat hearts for 25 min with Krebs–Henseleit buffer resulted in nearly constant release of ANP. Addition of oxytocin (10−6 M) significantly stimulated ANP release, and an oxytocin receptor antagonist (10−7 and 10−6 M) caused dose-related inhibition of oxytocin-induced ANP release and in the last few minutes of perfusion decreased ANP release below that in control hearts, suggesting that intracardiac oxytocin stimulates ANP release. In contrast, brain natriuretic peptide release was unaltered by oxytocin. During perfusion, heart rate decreased gradually and it was further decreased significantly by oxytocin (10−6 M). This decrease was totally reversed by the oxytocin antagonist (10−6 M) indicating that oxytocin released ANP that directly slowed the heart, probably by release of cyclic GMP. The results indicate that oxytocin receptors mediate the action of oxytocin to release ANP, which slows the heart and reduces its force of contraction to produce a rapid reduction in circulating blood volume.

A new class of obesity genes encodes leukocyte adhesion receptors

Obesity is a complex disease, and multiple genes contribute to the trait. The description of five genes (ob, db, tub, Ay, and fat) responsible for distinct syndromes of spontaneous monogenic obesity in mice has advanced our knowledge of the genetics of obesity. However, many other genes involved in the expression of this disease remain to be determined. We report here the identification of an additional class of genes involved in the regulation of adipose tissue mass. These genes encode receptors mediating leukocyte adhesion. Mice deficient in intercellular adhesion molecule-1 became spontaneously obese in old age on normal mouse chow or at a young age when provided with a diet rich in fat. Mice deficient in the counterreceptor for intercellular adhesion molecule-1, the leukocyte integrin αMβ2 (Mac-1), showed a similar obesity phenotype. Since all mice consumed approximately the same amount of food as controls, the leukocyte function appears to be in regulating lipid metabolism and/or energy expenditure. Our results indicate that (i) leukocytes play a role in preventing excess body fat deposition and (ii) defects in leukocyte adhesion receptors can result in obesity.