Kam F. Fok
Monsanto
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Featured researches published by Kam F. Fok.
Biochemical and Biophysical Research Communications | 1989
Grahame E. Pratt; Dan E. Farnsworth; Ned R. Siegel; Kam F. Fok; René Feyereisen
A peptide (allatostatin) causing strong and rapid inhibition of juvenile hormone synthesis in vitro by corpora allata from reproductively active females has been isolated from brain/retrocerebral complexes of the cockroach Diploptera punctata. The primary structure of this 13-residue peptide has been determined: Ala-Pro-Ser-Gly-Ala-Gln-Arg-Leu-Tyr-Gly-Phe-Gly-Leu-NH2. Removal of the terminal amide group caused at least a ten thousandfold loss of activity. This neurohormone has no sequence similarity with any other known neuropeptide. Its target in the biosynthetic pathway is located prior to the conversion of farnesol to juvenile hormone.
Biochemical and Biophysical Research Communications | 1984
David M. Geller; Mark G. Currie; K. Wakitani; Barbara R. Cole; Steven P. Adams; Kam F. Fok; Ned R. Siegel; S.R. Eubanks; G.R. Galluppi; Philip Needleman
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.
FEBS Letters | 1992
Roger C. Wiegand; Johji Kato; Margaret Huang; Kam F. Fok; James F. Kachur; Mark G. Currie
Guanylin is a mammalian peptide homologue of heat‐stable enterotoxins that acts on intestinal guanylate cyclase to elicit an increase in cyclic GMP. We have isolated a cDNA encoding an apparent precursor of guanylin from a human intestinal cDNA library. The mRNA is expressed at high levels in human ileum and colon. Human guanylin stimulated increases in T84 cell cyclic GMP levels, displaced 125I‐labelled heat‐stable enterotoxin (STa) binding to this cell line, and stimulated increases in short‐circuit current (Isc) or isolated rat proximal colonic mucosa. This peptide may play a role in regulating fluid and electrolyte absorption in human intestines.
Circulation Research | 1985
Korekiyo Wakitani; Takeshi Oshima; Arthur D. Loewy; Sandra W. Holmberg; Barbara R. Cole; Steven P. Adams; Kam F. Fok; Mark G. Currie; Philip Needleman
The atriopeptins are potent relaxants of norepinephrine-constricted aortic strips or are dilators of renal blood vessels in isolated perfused rat kidneys that are constricted by norepinephrine. This vasorelaxant property of the atriopeptins requires the presence of phenylalanine arginine (i.e., atriopeptin II, III, or ser-leu-arg-arg atriopeptin III) residues in the carboxy terminus which are considerably more effective than atriopeptin I (the 21 amino acid peptide which lacks the phe-arg C-terminus) or the core peptide (residues 3–19). However, these artificially in vitro precontracted preparations do not accurately predict the vascular effectiveness of the atriopeptins in intact rats. Intravenous administration of the atriopeptins (including atriopeptin I) to anesthetized rats produces concentration-dependent hypotension, a selective decrease in renal resistance in low doses (determined with microspheres), and pronounced diuresis. At higher doses, atriopeptins increase blood flow in other vascular beds. On the other hand, in the anesthetized dog, injection (intraarterially) of the phe-arg-containing peptides produces a concentration- dependent increase in both renal blood flow and sodium excretion, whereas atriopeptin I is inactive. Although there is a species difference in responsiveness to atriopeptin I, these data demonstrate a direct correlation between the renal vasodilation and diuresis produced by this novel family of atrial peptides.
European Journal of Pharmacology | 1989
Song Ping Han; Angelo J. Trapani; Kam F. Fok; Thomas C. Westfall; Mark M. Knuepfer
Endothelin is a potent vasoactive peptide in anesthetized rats and isolated vascular smooth muscle. This study was performed to describe the hemodynamic effects of endothelin in conscious, freely moving rats. Endothelin (0.067-2 nmol/kg i.v.) produced long-lasting, dose-dependent increases in arterial pressure, mesenteric and, to a lesser degree, hindquarters vascular resistances and decreases in heart rate. We suggest that endothelin may play an important role in regulation of arterial pressure by modulating peripheral vasomotor tone.
Biochemical and Biophysical Research Communications | 1988
Glen L. Hortin; Beverly Gibson; Kam F. Fok
alpha 2-Antiplasmin (AP) inhibits plasmin in a two-step reaction in which AP reversibly binds to lysine-binding sites of plasmin and, then, more slowly complexes covalently with the enzymes active site. Here, we show that the C-terminal lysine residue of AP has a key role in binding of the inhibitor to plasmin. A synthetic peptide corresponding to the C-terminal 26 amino acid residues of AP blocked association of AP with plasmin, but this activity of the peptide was lost when its C-terminal lysine residue was removed with carboxypeptidase B. The essential role of this lysine residue was shown more directly by treating AP with carboxypeptidase B and observing that AP lost its ability to inhibit plasmin rapidly.
Biochemical and Biophysical Research Communications | 1984
D.M. Gelher; Mark G. Currie; Ned R. Siegel; Kam F. Fok; Steven P. Adams; Philip Needleman
The high molecular weight fraction ( atriopeptigen -APG) obtained by gel filtration chromatography of rat atrial extracts was fractionated by isoelectric focusing and reverse phase HPLC to obtain a pure APG. Purification of cyanogen bromide digests of the crude high molecular weight fraction resulted in the isolation of a single biologically active cyanogen bromide cleavage peptide. Sequence analyses of these peptides coupled with recent reports of sequence analyses of intermediate molecular weight atrial peptides ( Thibault , et al. (1984) FEBS Letters 167, 352-356, and Kangwa , et al., Biochem. Biophys. Res. Commun 119, 933-940) provide the complete primary structure of an 111 residue APG.
Biochemical and Biophysical Research Communications | 1989
Ellen G. Mcmahon; Kam F. Fok; William M. Moore; Christine E. Smith; Ned R. Siegel; Angelo J. Trapani
We investigated whether big endothelin (porcine 1-40) had contractile activity in isolated rat aorta or pressor activity when injected intravenously into the anesthetized rat. When isolated rat aorta was exposed to a 100 nM concentration of big endothelin, 4.8% of a maximal KCl contraction was observed, compared to 131% of KClmax when paired aortic rings were exposed to an equivalent concentration of synthetic endothelin. Likewise, big endothelin had very weak pressor activity when injected intravenously into anesthetized, ganglion-blocked rats at 10 nmol/kg. When big endothelin was incubated with chymotrypsin, native endothelin and other peptide fragments were formed. Chymotrypsin-treated big endothelin produced an endothelin-like contraction when applied to isolated rat aortic rings, and a characteristic endothelin-like effect on blood pressure in vivo. Our results indicate that the biological activity of endothelin could be effectively blocked by inhibiting the enzyme which converts big endothelin to endothelin.
Life Sciences | 1990
Songping Han; Mark M. Knuepfer; Angelo J. Trapani; Kam F. Fok; Thomas C. Westfall
Snake venom-derived sarafotoxin S6B (SRT) and porcine endothelium-derived endothelin-1 (ET) have striking structural similarities. In conscious, freely-moving rats, ET (0.67 nmol/kg) produced a transient tachycardia and fall in arterial blood pressure which was followed by a long-lasting increase in arterial pressure, bradycardia, decrease in cardiac output (CO) and marked increase in total peripheral resistance. In contrast, SRT (0.67 nmol/kg) produced only the sustained cardiovascular responses. The sustained cardiovascular effects of SRT or ET were similarly attenuated by nifedipine. SRT and ET (30 nM) produced vasoconstriction in the isolated perfused mesenteric vascular bed without initial vasodilation. SRT and ET had potent positive inotropic and negative chronotropic effects on isolated perfused hearts and induced toxic reactions including coronary vasospasm, arrhythmias, A-V block and ventricular fibrillation. In addition to SRT lacking the initial depressor response in vivo, several differences in the activities of the peptides were also observed. ET produced greater and longer-lasting actions than SRT in producing pressor and vasoconstrictor responses in all 3 preparations, and in its ability to induce toxic effects on the heart.
Biochemical and Biophysical Research Communications | 1985
Nobuo Katsube; K. Wakitani; Kam F. Fok; Foe Siong Tjoeng; Mark E. Zupec; S.R. Eubanks; Steven P. Adams; Philip Needleman
Natriuretic-diuretic and vasodilator activities of synthetic atriopeptin (AP)-related peptides were examined in the anesthetized dog. We have selected, the naturally occurring, APIII as the reference compound for comparison with various related peptides. APIII is a 24 amino acid peptide with the sequence ser-ser-cys-phe-gly-gly-arg-ile-asp-arg-ile-gly-ala-gln-ser-gly-leu-gly- cys-asn-ser-phe-arg-tyr-OH. APII, another peptide isolated from atrial extracts, lacks the C-terminal arg- of APIII. N-terminal amino acid extensions on APIII or APII, exhibited enhanced natriuretic-diuretic effectiveness. Furthermore, the maximum response obtained by ser-leu-arg-arg-APIII and arg-arg-APIII were significantly higher and the dose-response curve was not parallel to that obtained with APIII. In contrast, there were no significant qualitative or quantitative differences between the renal blood flow responses produced by the N-terminal extended peptides and APII or APIII. These results suggest a heterogeneity of AP receptors in vascular and renal tubular tissues.