Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously observed, using a relatively primitive assay, that small oral doses (on the order of 1 microgram = 1 nmol = 1000 pmol per rat) of vasopressin can produce antidiuresis in hydrated rats, and that the oral activity was enhanced by simultaneous administration of an inhibitor of intestinal proteolysis. A more sensitive semi-automated computer-linked apparatus was used to conveniently and quickly compare the antidiuretic activities of the two natural and one synthetic vasopressin peptides by several routes of administration. (The approximate dose in pmol that resulted in a 50% decrease in urine flow is indicated in square brackets.) Intravenous lysine vasopressin was used as the benchmark dose [5]. Arginine and lysine vasopressin [3500], and the synthetic analogue, 1-deamino-8-D-arginine vasopressin (DDAVP) [20], were active by oral administration. The oral activities of arginine and lysine vasopressin were always enhanced by the simultaneous administration of aprotinin [1000], a natural inhibitor of trypsin; the effect of aprotinin on the oral activity of DDAVP was inconsistent. The vasopressins were more active when administered by the rectum: arginine vasopressin [20] and DDAVP [10]. The rectal activities of the peptides were increased by the absorption adjuvant, 5-methoxysalicylate (arginine vasopressin [10]; DDAVP [0.5]). The vasopressin peptides were also delivered by mouth in an impermeable coating of an azoaromatic cross-linked polymer, which is degraded by bacteria in the colon, to release the peptides in the upper colon for absorption (lysine vasopressin [525]).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasopressin: a model for the study of effects of additives on the oral and rectal administration of peptide drugs. 334 21

In order to elucidate the mechanism(s) responsible for the prolonged antidiuretic activity of 1-deamino-[8-D-arginine]-vasopressin (dDAVP), antidiuretic activities of dDAVP and arginine vasopressin (AVP) were determined in the rat following either oral administration or incubation with AVP-degrading enzymes and reagents. Oral administration of dDAVP to conscious water-loaded rats resulted in significant antidiuresis while AVP resulted in slight and transient antidiuresis. In the ethanol anesthetized water-loaded rats, antidiuretic activities of 136pg of AVP and 50pg of dDAVP, which were found to be equipotent, were compared after incubation with digestive enzymes (pepsin, trypsin, alpha-chymotrypsin), late pregnancy plasma, or sodium thioglycollate. The antidiuretic activity of AVP was completely destroyed by 30-min incubation with trypsin, alpha-chymotrypsin, or late pregnancy plasma and almost all AVP was inactivated by 0.2 M sodium thioglycollate. On the other hand, the antidiuretic activity of dDAVP was not destroyed by trypsin or pregnancy plasma but was partly destroyed by alpha-chymotrypsin and sodium thioglycollate. Neither the antidiuretic activity of AVP nor that of dDAVP was affected by pepsin. Thus, the antidiuresis observed after oral administration of dDAVP might be brought about by the resistance to digestive enzymes. Furthermore, the resistance of dDAVP to digestive enzymes, late pregnancy plasma and sodium thioglycollate might be responsible for the prolonged antidiuretic action of dDAVP in vivo.
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PMID:Resistance of 1-deamino-[8-D-arginine]-vasopressin to in vitro degradation as compared with arginine vasopressin. 393 2