David M. Geller

Atriopeptins as Cardiac Hormones

P Needleman, SP Adams, BR Cole, MG Currie, DM Geller, ML Michener, CB Saper, D Atriopeptins as cardiac hormones ISSN: 1524-4563 Copyright

Atriopeptins: A family of potent biologically active peptides derived from mammalian atria

Extracts of rat atria are potent stimulators of sodium and urine excretion, and relax vascular and intestinal smooth muscle preparations. The structures of six biologically active peptides obtained from atrial extracts are reported here. Ion exchange chromatography of a low molecular weight fraction obtained by gel filtration of atrial extracts produced two natriuretic fractions: the first induced relaxation of intestinal smooth muscle strips only, whereas the second also relaxed vascular strips as well. From the first fraction four pure biologically active peptides obtained by reverse phase HPLC have been sequenced: the 21 amino acid peptide, designated atriopeptin I, and three homologs (des- ser1 -, des- ser1 -ser2-, and des- ser21 - atriopeptin I). From the second fraction two pure biologically active peptides were obtained, which had C-terminal extensions of atriopeptin I: atriopeptins II (23 amino acid residues) and III (24 residues), having respectively phe-arg and phe-arg-tyr C-termini. These results suggest that this family of six peptides, sharing the same 17 membered ring formed by an internal cystine disulfide, is derived from a common high molecular weight precursor.

Atriopeptin release from the isolated perfused rabbit heart

Mammalian atrial extracts have been shown to contain bioactive peptides which exert natruiretic, diuretic, and smooth muscle relaxant effects. These extracts include several low molecular weight (less than 5,000 Mr) atrial peptides (atriopeptins) which exhibit identical sequences over a central core region which are derived from the high molecular weight peptide (atriopeptigen) precursor which has been purified and sequenced. In the current study we found that extracts of rabbit atria possess both high and low molecular weight bioactive atrial peptides, however, the coronary venous effluent obtained from the isolated perfused rabbit heart only contained the low molecular weight peptide. This trypsin labile activity causes a dose-dependent relaxation of rabbit aorta and chicken rectum assay strips. Separation of the bioactivity with gel filtration chromatography and reversed phase HPLC indicates the heart releases a single substance similar to atriopeptin III. There was no evidence that atriopeptigen was released from the isolated perfused rabbit heart. We suggest that atriopeptigen is proteolytically processed in the atria to an atriopeptin which is subsequently the released form of the atrial peptide.

Bovine microsomal albumin: amino terminal sequence of bovine proalbumin.

Abstract Bovine liver microsomes contain an albumin having an apparent isoelectric point approximately 0.3 pH unit in excess of bovine serum albumin. Sequence analysis of the purified protein shows that the first ten residues at the amino terminus are: Arg-Gly-Val-Phe-Arg-Arg -Asp-Thr-His-Lys. The data suggest that the hexapeptide (underlined), identical to that found in proalbumin from rat liver, is attached to the amino terminus of bovine serum albumin (the last four residues). By analogy with the rat liver system, this protein therefore is bovine proalbumin, a precursor of bovine serum albumin.

Kallikrein activation of a high molecular weight atrial peptide

Mammalian atrial extracts contain bioactive peptides that exert profound effects upon renal function and isolated smooth muscle preparations. Gel filtration chromatography of rat atrial extract separates the activity into two peaks having apparent molecular weights of 20,000 to 30,000 and less than 10,000. Mild proteolytic treatment (trypsin 1 U/ml) of the high molecular weight fraction enhances the smooth muscle relaxant activity of this fraction and concomitantly reduces the apparent molecular weight of this fraction to less than 10,000. In this report we show that urinary and submaxillary kallikrein enhances the activity of rat atrial extracts in a similar fashion. Pretreatment of the high molecular weight fraction with either kallikrein (1 microgram/ml) enhances the smooth muscle relaxant activity of this fraction. Similar treatment of the low molecular weight fraction had no effect. The enhancement of the bioactivity of the high molecular weight substance(s) by the kallikreins was abolished by aprotinin but was unaffected by soybean trypsin inhibitor. These results suggest that exogenous addition of tissue kallikrein activates a high molecular weight peptide by limited proteolysis. Analysis of the kallikrein-treated high molecular weight peptide fraction by gel filtration indicates that the biological activity comigrates with the low molecular weight peptides present in the original atrial extract.

Atriopeptins: potential mediators of an endocrine relationship between heart and kidney

Abstract Homeostatic regulation of fluid and electrolyte balance is essential for survival. The kidney plays a primary role in determining the composition and volume of body fluids. Although numerous factors which regulate this homeostatic balance have been analysed, the humoral control of sodium excretion has been elusive. In this review Philip Needleman and his colleagues deal with the very recent identification of a novel family of peptides - atriopeptins I, II and III - present in the heart that have the capacity to modulate renal and vascular function. They also discuss the future.

Rat serum albumin biosynthesis: Evidence for a precursor

Summary An albumin-like protein (pro-albumin) has been isolated from rat liver microsomal albumin by isoelectric focusing. Unlike intracellular serum albumin, it becomes highly radioactive in the course of albumin biosynthesis at the expense of labeled amino acids in vivo . The albumin-like protein is immunologically indistinguishable from rat serum albumin and has the same (or similar) N-terminus: glutamate (or glutamine). Maps of tryptic peptides suggest that the albumin-like protein may be a peptide derivative of serum albumin.

Chicken microsomal albumin: Amino terminal sequence of chicken proalbumin

Abstract Chicken liver microsomes contain an albumin having an isoelectric point approximately 0.2 pH unit in excess of that of chicken serum albumin. Although the serum protein is also present in microsomes, only the basic albumin there becomes labelled and undergoes turnover in vivo . Sequence analysis of the purified basic microsomal albumin indicates that the first twelve residues are: Arg-Asn-Leu-Gln-Arg-Met-Ala-Arg -Asp-Ala-Glu-His . The data suggest that the octapeptide (underlined) is attached to the amino terminus of chicken serum albumin (the last four residues). The amino terminal sequence of the serum albumin precursor in chicken liver is thus markedly different from that of the rat and bovine proalbumins.

Identification of the cardiac and circulating form of atriopeptin in rabbit

Analysis of peptides purified from high and low molecular weight fractions of rabbit atrial extracts indicates that the sequence of the first 30 residues of rabbit atriopeptigen exhibits 80% homology with the rat peptide, and that the low molecular weight rabbit peptide (28 residues) is identical to rat atriopeptin 28 (AP 28). The effects of infused 1-deaminoarginine8-vasopressin (dAVP) and phenylephrine, volume expansion, and water immersion on AP release into the circulation of the rabbit was studied. Neither dAVP, nor water immersion elevated right atrial pressure (RAP) or plasma AP levels in the anesthetized rabbits. Phenylephrine induced a sustained increase in systemic blood pressure and right atrial pressure which was accompanied by elevated plasma AP immunoreactivity which appeared to be identical to rat AP-28 on HPLC. There is obviously a preferential conservation of the AP sequence, since the C-terminal peptide is exactly the same in rabbit, rat and mouse and differs from human, dog, cow and pig only by the single substitution of an isoleucine for a methionine residue.

Kinetics of light-induced absorbance changes in Rhodospirillum rubrum extracts☆

Abstract This paper is a report of the kinetics of absorbance changes induced in extracts of R. rubrum during and following infrared illumination ( Smith and Baltscheffsky, 1959 , Geller and Lipmann, 1960 ). R. rubrum extracts, purified by a novel procedure, show absorbance changes which are modified strikingly in the course of activation of photophosphorylation. The effects suggest that common components may be involved in both the absorbance changes and photophosphorylation.