radiology procedures to neutralize the anti-clotting effects of heparin. Adverse effects include increased pulmonary artery pressure and decrease peripheral blood pressure, myocardial oxygen consumption, cardiac output, and heart rate. Protamine sulfate is an antidote for heparin overdose, but severe allergy may occur. A chain shortened version of protamine also acts as a potent heparin antagonist, but with markedly reduced antigenicity. It was initially produced as a mixture made by thermolysin digestion of protamine, but the actual effective peptide portion VSRRRRRRGGRRRR has since been isolated. An analogue of this peptide has also been produced. In gene therapy, protamine sulfate's ability to condense plasmid DNA along with its approval by the U.S. Food and Drug Administration (FDA) have made it an appealing candidate to increase transduction rates by both viral and nonviral (e.g. utilizing cationic liposomes) mediated delivery mechanisms. Protamine may be used as a drug to prevent obesity. Protamine has been shown to deter increases in body weight and low-density lipoprotein in high-fat diet rats. This effect occurs through the inhibition of lipase activity, an enzyme responsible for triacylglycerol digestion and absorption, resulting in a decrease in the absorption of dietary fat. No liver damage was found when the rats were treated with protamine. However, emulsification of long-chain fatty acids for digestion and absorption in the small intestine is less constant in humans than rats, which will vary the effectiveness of protamine as a drug. Furthermore, human peptidases may degrade protamine at different rates, thus further tests are required to determine protamine's ability to prevent obesity in humans. Species distribution and isoforms Mice, humans and certain fish have two or more different protamines, whereas the sperm of bull and boar, have one form of protamine due to a mutation in the PRM2 gene. In the rat, although the gene for PRM2 is present, expression of this protein is extremely small because of limited transcription due to an inefficient promoter in addition to altered processing of the mRNA transcript. Mammals The 2 human protamines are denoted PRM1 and PRM2. In mice and humans, PRM1, PRM2, and TNP2 are co-located in a conserved gene cluster. Eutherian mammals generally have both PRM1 and PRM2. Metatherians on the other hand only have a homolog to P1. Fish Examples of protamines from fish are: salmine and protamine sulfate from salmon clupeine from herring sperm (Clupea) iridine from rainbow trout thinnine from tunafish (Thunnus) stelline from starry