Publisher Summary This chapter discusses the structural and functional characterization of anaphylatoxins, spasmogenic substances released during complement activation. These low molecular weight peptide fragments of C3 and C5 elicit a variety of cellular responses, which implies that they play a significant role in inflammation and acute allergic reactions. Their stimulation of multiple cell types at pico- and femtomolar concentrations suggests a hormone-like action via specific cell surface receptors. By using the information available defining the amino acid sequences of these molecules it is possible to synthesize oligopeptides with the properties of anaphylatoxins and these compounds serve as effective tools for analyzing further the mechanism(s) by which these potent substances function. They are functionally defined by their actions on the vasculature, smooth muscle, mast cells, and certain types of peripheral blood cells. The most important contribution of anaphylatoxin research to biology is the realization that complement reaction products act as hormone-like messengers that profoundly affect the function of certain cells. A variety of cell types is activated by the complement reaction products C3a and C5a, whether they are acting as spasmogens, chemotaxins, or cause release reactions.

Anaphylatoxins: C3a and C5a.

The blood-bathed organ technique has been used to demonstrate that angiotensin I is converted to angiotensin II in the lungs, but not in other vascular beds. The results do not support hypotheses which suggest a completely intra-renal role for the renin–angiotensin system.

Fate of Angiotensin I in the Circulation

Purification and characterization of enkephalin convertase, an enkephalin-synthesizing carboxypeptidase.

THE KIDNEY contains several hormonal systems—kallikrein-kinin, renin-angiotensin, prostaglandin—which serve as renal self-regulatory mechanisms and may have extrarenal effects as well. Although the functions of the kallikrein-kinin system are incompletely defined, there is evidence that it may regulate renal blood flow, modulate tubular salt and water transport, and participate in the pathogenesis of a number of human diseases, such as hypertension. Unfortunately, many components of the renal kallikrein-kinin system are not adequately characterized and many current assays are of uncertain specificity. Hence, at present we must be cautious in interpreting available observations. Greater awareness of the potential physiological and clinical importance of the renal kallikrein-kinin system has led to increased research in this area. Recent progress in purification of components and in development of more specific assays should lead to important insights in the near future. Because this is a rapidly evolving field, it is important to note that this review was completed in July, 1978. To limit the reference list within the compass of a Brief Review, only relatively recent references are cited in most cases, even if original or older investigations are more extensive.

The renal kallikrein-kinin system.

COHN fraction IV-1 of human plasma contains an enzyme, carboxypeptidase N, which inactivates bradykinin and kallidin1,2 and also cleaves smaller substrates such as hippuryl-L-lysine (HLL)3. The kininase also has an esterase activity—it hydrolyses the ester substrate hip-puryl-L-argininic acid (HLAa)4, For the sake of simplicity in this communication, we shall refer to this enzyme as kininase I.

I.M. Wohler

Papers

Carboxypeptidase in blood and other fluids—I.: Properties, distribution, and partial purification of the enzyme