Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations.
Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine-or taurine-conjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probable attributable to their bile salt contaminants.
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology*; D002793:Cholic Acids / Q000494:pharmacology; D002855:Chromatography, Thin Layer; D003840:Deoxycholic Acid / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D051381:Rats; D012633:Secretin / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000201:enzymology
D001647:Bile Acids and Salts; D002793:Cholic Acids; D003840:Deoxycholic Acid; D002635:Chenodeoxycholic Acid; D012633:Secretin; D002766:Cholecystokinin; D006162:Guanylate Cyclase