Catabolism of rat growth hormone-releasing factor(1–29) amide in rat serum and liver

Boulanger, Luce; Roughly, Peter; Gaudreau, Pierrette

doi:10.1016/0196-9781(92)90173-z

Cited by 28 publications

(9 citation statements)

References 30 publications

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“…GRF is rapidly degraded in vivo, both by enzymic and chemical pathways, its half-life being between 10 and 20 min (Su et al 1991, Boulanger et al 1992). The principle means of GRF inactivation is by the widely distributed dipeptidyl peptidase IV which cleaves GRF between alanine 2 and aspartate 3 (Campbell et al 1994).…”

Section: Discussionmentioning

confidence: 99%

Immuno-enhancement and -inhibition of GH-releasing factor by site-directed anti peptide antibodies in vivo and in vitro

Pell

James²

1995

Journal of Endocrinology

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It is now well established that specific antibodies and binding proteins can potentiate rather than inhibit hormone activity. In order to investigate this phenomenon further, the current study was undertaken using a hormone with a characterised structure, in terms of receptor binding, and for which activity has already been manipulated in specific ways (prolongation of half-life, increased receptor affinity) using synthetic hormone analogues. GH-releasing factor (GRF) is a 40 or 44 residue peptide and is, together with somatostatin, responsible for the regulation of GH secretion. The effects of site-directed anti peptide antibodies were determined on the activity of GRF in vivo and in vitro as GH release. The peptide regions of GRF were: 1-14 (part of putative receptor-binding region) and 31-44 and 35-44 (sites thought to be distant from the receptor-binding region). Five sheep were administered GRF (1 microgram/kg), anti peptide immunoglobulin (Ig; a calculated tenfold excess binding to GRF dose), or GRF together with anti peptide Ig (preincubated for 1 h). GRF induced a significant increase in plasma GH concentration over the next 240 min, this was abolished when GRF was administered with anti 1-14 Ig (P < 0.05) and augmented (P < 0.05) when GRF was administered with anti 35-44 Ig; anti 31-44 had no effect on GRF activity. Anti 35-44 Ig alone induced an increase in GH secretion which was equivalent to that for GRF alone, implying that the antibody had interacted and potentiated with endogenous GRF. The Ig effects on exogenous GRF activity were confirmed for GH release in vitro using primary cultures of sheep pituitary cells, except that anti 31-44 Ig also augmented GH release (P < 0.05) when co-administered with GRF. (ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussionmentioning

confidence: 99%

Immuno-enhancement and -inhibition of GH-releasing factor by site-directed anti peptide antibodies in vivo and in vitro

Pell

James²

1995

Journal of Endocrinology

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“…DPP IV is found in plasma and is also localized on the surface of capillary endothelial cells, at kidney brush-border membranes, on the surface of hepatocytes, on the surface of some T-lymphocyte subpopulations, and on thymocytes (Loijda 1979, Mentlein et al 1984, Nausch & Heymann 1985, McCaughan et al 1990). DPP IV is responsible for degradation and inactivation of several biologically active peptides such as substance P (Ahmad et al 1992), growth-hormone-releasing factor (Frohmann et al 1989, Boulanger et al 1992, gastric inhibitory peptide/glucosedependent insulinotropic peptide (Mentlein et al 1993) and peptide histidine methionine (PHM) (Mentlein et al 1993). All these peptides share considerable sequence similarity at their N-termini since they start with either His-Ala-or Tyr-Ala-.…”

Section: Discussionmentioning

confidence: 99%

A synthetic glucagon-like peptide-1 analog with improved plasma stability

Ritzel

Leonhardt²,

Ottleben³

et al. 1998

Journal of Endocrinology

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Glucagon-like peptide-1 (GLP-1) is the most potent endogenous insulin-stimulating hormone. In the present study the plasma stability and biological activity of a GLP-1 analog, [Ser 8 ]GLP-1(7-36)amide, in which the second N-terminal amino acid alanine was replaced by serine, was evaluated in vitro and in vivo. Incubation of GLP-1 with human or rat plasma resulted in degradation of native GLP-1(7-36)amide to GLP-1(9-36)amide, while [Ser 8 ]GLP-1(7-36)amide was not significantly degraded by plasma enzymes. Using glucose-responsive HIT-T15 cells, [Ser 8 ]GLP-1(7-36)amide showed strong insulinotropic activity, which was inhibited by the specific GLP-1 receptor antagonist exendin-4(9-39)amide. Simultaneous i.v. injection of [Ser 8 ]GLP-1(7-36)amide and glucose in rats induced a twofold higher increase in plasma insulin levels than unmodified GLP-1(7-36)amide with glucose and a fivefold higher increase than glucose alone.[Ser 8 ]GLP-1(7-36)amide induced a 1·5-fold higher increase in plasma insulin than GLP-1(7-36)amide when given 1 h before i.v. application of glucose. The insulinotropic effect of [Ser 8 ]GLP-1(7-36)amide was suppressed by i.v. application of exendin-4(9-39)amide. The present data demonstrate that replacement of the second N-terminal amino acid alanine by serine improves the plasma stability of GLP-1(7-36)amide. The insulinotropic action in vitro and in vivo was not impaired significantly by this modification.

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“…The enzyme has been shown to be responsible for the degradation and inactivation of circulating peptides with penultimate proline, like substance P (Heymann and Mentlein, 1978;Ahmad et al, 1992), but also for growth-hormonereleasing factor (GRF) with penultimate alanine (Frohman et al, 1989;Kubiak, 1989;Boulanger et al, 1992).…”

Section: Institut Olshausenstrasse 40-60 D-24118 Kiel Germanymentioning

confidence: 99%

Dipeptidyl‐peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon‐like peptide‐1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum

Mentlein

Gallwitz

Schmidt

1993

European Journal of Biochemistry

1,083

655

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Anatomisches Institut andPeptides of the glucagodvasoactive-intestinal-peptide (VIP) peptide family share a considerable sequence similarity at their N-terminus. They either start with Tyr-Ala, His-Ala or His-Ser which might be in part potential targets for dipeptidyl-peptidase IV, a highly specialized aminopeptidase removing dipeptides only from peptides with N-terminal penultimate proline or alanine. Growthhormone-releasing factor(1-29)amide and gastric inhibitory peptidefglucose-dependent insulinotropic peptide (GIP) with terminal Tyr-Ala as well as glucagon-like peptide-1 (7 -36)amidehnsulinotropin [GLP-l(7 -36)amidel and peptide histidine methionine (PHM) with terminal His-Ala were hydrolysed to their des-Xaa-Ala derivatives by dipeptidyl-peptidase IV purified from human placenta. VIP with terminal His-Ser was not significantly degraded by the peptidase. The kinetics of the hydrolysis of GIP, GLP-1(7-36)amide and PHM were analyzed in detail. For these peptides K, values of 4-34 pM and V,,, values of 0.6-3.8 pmol . min-' . mg protein-' were determined for the purified peptidase which should allow their enzymic degradation also at physiological, nanomolar concentrations. When human serum was incubated with GIP or GLP-1(7-36)amide the same fragments as with the purified dipeptidyl-peptidase IV, namely the des-Xaa-Ala peptides and Tyr-Ala in the case of GIP or His-Ala in the case of GLP-1(7-36)amide, were identified as the main degradation products of these peptide hormones. Incorporation of inhibitors specific for dipeptidylpeptidase IV, 1 mM Lys-pyrrolidide or 0.1 mM diprotin A (Ile-Pro-Ile), completely abolished the production of these fragments by serum. It is concluded that dipeptidyl-peptidase IV initiates the metabolism of GIP and GLP-1(7-36)amide in human serum. Since an intact N-terminus is obligate for the biological activity of the members of the glucagonNIP peptide family [e. g. ) is known to be inactive to release insulin in the presence of glucose as does intact GIP], dipeptidylpeptidase-IV action inactivates these peptide hormones. The relevance of this finding for their inactivation and their determination by immunoassays is discussed.

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Catabolism of rat growth hormone-releasing factor(1–29) amide in rat serum and liver

Cited by 28 publications

References 30 publications

Immuno-enhancement and -inhibition of GH-releasing factor by site-directed anti peptide antibodies in vivo and in vitro

Immuno-enhancement and -inhibition of GH-releasing factor by site-directed anti peptide antibodies in vivo and in vitro

A synthetic glucagon-like peptide-1 analog with improved plasma stability

Dipeptidyl‐peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon‐like peptide‐1(7–36)amide, peptide histidine methionine and is responsible for their degradation in human serum

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