The Influence of Enzymes on Neurohypophysial Hormones and Similar Peptides

Tuppy, H.

doi:10.1007/978-3-642-46127-9_3

Cited by 21 publications

(18 citation statements)

References 170 publications

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“…Present results on AVP are in line with the previous findings that antidiuretic activity of AVP was eliminated by trypsin and achymotrypsin, but not by pepsin (Sawyer 1967;Tuppy 1968;Lauson 1974 incubation with late pregnancy plasma. Late pregnancy plasma has been reported to contain a cystine aminopeptidase, vasopressinase or oxytocinase, which inactivates AVP and oxytocin by splitting the bond between the amino-terminal hemicystine and tyrosine at positions 1 and 2 (Tuppy 1968;Walter and Simmons 1977).…”

Section: Discussionsupporting

confidence: 92%

“…Late pregnancy plasma has been reported to contain a cystine aminopeptidase, vasopressinase or oxytocinase, which inactivates AVP and oxytocin by splitting the bond between the amino-terminal hemicystine and tyrosine at positions 1 and 2 (Tuppy 1968;Walter and Simmons 1977). Accordingly, it is likely that deamination of hemicystine at position 1 causes resistance to the action of vasopressinase.…”

Section: Discussionmentioning

confidence: 99%

“…Sodium thioglycollate has been shown to inactivated AVP by splitting the disulfide bridge of AVP (Tuppy 1968;Vorherr et al, 1968;Lauson 1974). In the present study, only about 30% of the antidiuretic activity of dDAVP was inactivated by sodium thioglycollate when that of AVP was almost completely inactivated.…”

Section: Discussionmentioning

confidence: 99%

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Resistance of 1-deamino-(8-D-arginine)-vasopressin to in vitro degradation as compared with arginine vasopressin.

et al. 1985

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

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Resistance of 1-deamino-(8-D-arginine)-vasopressin to in vitro degradation as compared with arginine vasopressin.

et al. 1985

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“…It is not excreted in the urine and it disappears from the bloodstream within 2-3 wk after delivery. The physiologic function of this enzyme system is not understood (6).…”

Section: Methodsmentioning

confidence: 99%

“…Oxytocin, AVP, LVP, and AVT are inactivated by incubation with each of the following: the oxytocinase-vasopressinase system of human pregnancy plasma, tyrosinase, and thioglycolate. These agents act by disrupting the peptide bonds between cystine and tyrosine, by the probable formation of an O-quinone group on tyrosine, and by disruption of the disulfide bond between the two cystine half-moieties, respectively (6). Although considerable evidence regarding structure can be adduced from such destruction experiments, a specific identification is never possible.…”

Section: Introductionmentioning

confidence: 99%

Identification of neurohypophysial hormones with their antisera

Vorherr¹,

Munsick²

1970

J. Clin. Invest.

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A B S T R A C T Identifying posterior pituitary hormones in body fluids or neurohypophysial extracts was heretofore partially achieved by using pharmacologic potency ratios or semispecific inactivation by thioglycolate or enzymes. Production of antisera against oxytocin and lysine-vasopressin has prompted us to test their specificity against lysine-vasopressin, arginine-vasopressin, arginine-vasotocin, and oxytocin. In ethanol anesthetized rats, antidiuretic and milk-ejection activities were assayed for each peptide-antiserum combination after 0, 30, 60, and 90 min of incubation. Results indicate that (a) oxytocin antiserum inactivates oxytocin, but not arginine-vasopressin, lysine-vasopressin, or arginine-vasotocin; vasopressin antiserum inactivates arginine-vasopressin and lysine-vasopressin, but neither oxytocin nor arginine-vasotocin; (b)) an identifiable antigenic site exists for each hormone; (c) relatively specific identifications of natural neurohypophysial peptides are possible using antisera and bioassays; (d) this method is promising for identifying neurohypophysial peptides in body fluids and pituitary extracts; and (e) active and passive immunization against oxytocin and vasopressin may increase our understanding of their physiologic functions.

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Oxytocin Verbindungen zur oralen Behandlung von Bauchschmerzen

Kremsmayr,

Schober,

Kaltenböck

et al. 2024

Angewandte Chemie

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Abdominal pain presents an onerous reality for millions of people affected by gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel diseases (IBD). The oxytocin receptor (OTR) has emerged as a new analgesic drug target with OTR expression upregulated on colon‐innervating nociceptors in chronic visceral hypersensitivity states, accessible via luminal delivery. However, the low gastrointestinal stability of OTR’s endogenous peptide ligand oxytocin (OT) is a bottleneck for therapeutic development. Here, we report the development of potent and fully gut‐stable OT analogues, laying the foundation for a new area of oral gut‐specific peptide therapeutics. Ligand optimisation guided by structure‐gut‐stability‐activity relationships yielded highly stable analogues (t1/2 >24 h, compared to t1/2 <10 min of OT in intestinal fluid) equipotent to OT (~3 nM) and with enhanced OTR selectivity. Intra‐colonic administration of the lead ligand significantly reduced colonic mechanical hypersensitivity in a concentration‐dependent manner in a mouse model of chronic abdominal pain. Moreover, oral administration of the lead ligand also displayed significant analgesia in this abdominal pain mouse model. The generated ligands and employed strategies could pave the way to a new class of oral gut‐specific peptides to study and combat chronic gastrointestinal disorders, an area with substantial unmet medical needs.

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The Influence of Enzymes on Neurohypophysial Hormones and Similar Peptides

Cited by 21 publications

References 170 publications

Resistance of 1-deamino-(8-D-arginine)-vasopressin to in vitro degradation as compared with arginine vasopressin.

Resistance of 1-deamino-(8-D-arginine)-vasopressin to in vitro degradation as compared with arginine vasopressin.

Identification of neurohypophysial hormones with their antisera

Oxytocin Verbindungen zur oralen Behandlung von Bauchschmerzen

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