UBC Theses and Dissertations
Kallikrein-kinin system in plasma of poikilotherm vertebrates Dunn, Rex Stewart
The little studied plasma kallikrein-kinin system of poikilotherm vertebrates was investigated in several species offish, amphibians, and reptiles, and compared to the well-known mammalian enzyme system. It was found that the plasmas of all fish and amphibians tested differed from reptilian and mammalian plasma in their inability to release a kinin-like factor when reacted with trypsin or glass, and no evidence was obtained to suggest that these plasmas contain enzymic machinery which can produce a kinin. However, it was shown that heat-denatured plasma from these animals did develop biological activity when treated with hog pancreas kallikrein, an enzyme specific for releasing kinins. Thus, the equivalent of a kininogen might exist in these plasmas. Since turtle plasma produced a kinin by endogenous enzymes, detailed studies of this system were conducted. By a variety of criteria, enzymic mechanisms for kinin production in this plasma were closely similar to those of mammalian plasma. However, purification of the turtle kinin released by endogenous enzymes, followed by pharmacological and chemical tests showed that this kinin was chemically different from bradykinin, its mammalian counterpart. Data obtained from amino acid analysis of the peptide, and from certain pharmacological tests, strongly suggested that the structure of turtle kininis 6-thr-bradykinin; i.e., that a threonine residue has been substituted for a serine . The possible significance of this finding is discussed. Preliminary studies of the pharmacological effects of bradykinin on aspects of blood pressure and flow in the turtle itself are described. Intra-arterial injections of bradykinin over a wide range of doses always produced a press or response which could be greatly reduced by adrenergic blockade. This is in contrast with the effect of, the peptide in mammals, where there is typically a hypotensive response which cannot be reduced by adrenergic blockade. The significance of this difference is discussed, and approaches to future investigations are suggested.
Item Citations and Data