Biotransformation of Neuropeptides

Griffiths, E.C.; McDermott, J.R.

doi:10.1159/000124039

Cited by 29 publications

(11 citation statements)

References 57 publications

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“…One possible explanation for these findings is that the median eminence secretes enzymes that selec tively degrade peptides. Neuropeptides are degraded by enzymatic cleavage in the brain [44] and the degradation of GnRH has been shown in the median eminence of the rat [45] and the sheep [46]. It seems most likely that the metalloendopeptidase EC.3.4.15 is one enzyme that de grades GnRH [47][48][49][50].…”

Section: Discussionmentioning

confidence: 99%

Many Peptides that Are Present in the External Zone of the Median Eminence Are Not Secreted into the Hypophysial Portal Blood of Sheep

et al. 1993

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Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y(NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.

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Section: Discussionmentioning

confidence: 99%

Many Peptides that Are Present in the External Zone of the Median Eminence Are Not Secreted into the Hypophysial Portal Blood of Sheep

et al. 1993

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“…Nevertheless, biotransformation of peptides in t h e i n t e s t i n e m a y p r o d u c e s h o r t e r a c t i v e polypeptides [16]. A previous study showed that enteral application of LHRH to rats had half of the intravenous LHRH response [17].…”

Section: Discussionmentioning

confidence: 99%

“…Up to now, oral application has been uncommon due to the low bioavailability after degradation of GnRH by buccal and intestine enzymes. Proteases, such as chymotrypsin, elastase and gastricsin, are responsible for GnRH degradation in the intestine [11][12][13][14] Metabolic breakdown of GnRH, however, may lead to biologically active fragments that can be absorbed through the intestine and produce biological effects in receptive tissues [15][16][17]. Furthermore, the order of degradability of GnRH agonists, e.g., D-Phe 6 -GnRH and D-Trp 3 -D-Phe 6 -GnRH, is lower compared to native GnRH [18].…”

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confidence: 99%

Study of Enteral versus Parenteral Application of the Gonadotropin Releasing Hormone Agonist Gonadorelin[6-D-Phe] (D-Phe6-LHRH) on LH Secretion in Goettinger Miniature Pigs

Brüssow

Kanitz

Tuchscherer

et al. 2007

Journal of Reproduction and Development

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Abstract. With respect to the assessment of residue situation and as a part of preclinical trials to determine the biological activities of potential gonadotropin releasing hormone (GnRH) residues in porcine organisms the GnRH agonist Gonadorelin[6-D-Phe] (D-Phe 6 -LHRH) was administered either enterally or intramuscularly (i.m.) to female Goettinger miniature pigs in order to evaluate the GnRHinduced luteinizing hormone (LH) surge. Gilts received an (i) enteral application of 10 mg D-Phe 6 -LHRH via a probang (enteral group, n=7), (ii) i.m. injection of 0.1 mg D-Phe 6 -LHRH (parenteral group, n= 5), or (iii) saline injection (control group, n=4). The GnRH and saline applications were repeated every second day with up to seven repetitions. Blood samples were collected via previously fitted jugular catheters immediately before injections, over an 8 h period in 1 h intervals beginning 2 h after injections, and at 24, 26, 28 and 30 h after applications. Enteral application of D-Phe 6 -LHRH induced an LH surge in 23 of 30 treatments. All gilts in the parenteral group exhibited LH release after each DPhe 6 -LHRH application (P<0.05), whereas no LH surges were observed after saline injection in the control group. A significant (P<0.05) LH rise to mean maximum LH concentrations of 3.25 ± 0.43 and 3.05 ± 0.26 ng/ml occurred in both the enteral and parenteral groups, but there was no difference in the time interval after GnRH (2.6 ± 0.3 vs. 2.3 ± 0.3 h) and the mean duration of LH peak (6.5 ± 0.4 and 6.8 ± 0.3 h) between the treatment groups. In conclusion, (i) enteral application of 10 mg D-Phe 6 -LHRH induced LH release in a physiological range from the pituitary of female minipigs, and (ii) neither an accumulative effect nor a cumulative LH response were found after repeated GnRH application. Furthermore, (iii) in regard to consumer protection and gonadotropin secretion, D-Phe 6 -LHRH residues can be excluded from having long-term effects.

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“…The clearance of NPY from human plasma has a half-life of approximately 20 minutes (35), but it is unknown whether renal, enzymatic or other mechanisms, or a combination of these, mediate the disappearance of NPY from systemic circulation. It has been demonstrated that neuropeptides are degraded by enzymatic cleavage in the brain and during passage through the hypophysial portal vessels (36). It seems most likely that endopeptidase 24.11 (dipeptidyl-peptidase IV) is one enzyme that degrades NPY and VIP (37)(38)(39).…”

Section: Discussionmentioning

confidence: 99%

The Neuropeptides, VIP and NPY, That Are Present in the Thyroid Nerves Are Not Released into the Thyroid Vein

Michalkiewicz¹,

Dey²,

Huffman³

et al. 1998

Thyroid

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In the present study, we tested the hypothesis that the neuropeptides, vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY), which are present in the thyroid nerves, act as physiological neurotransmitters involved in the regulation of thyroid hormone secretion and thyroid blood flow. Specifically, we examined whether these neuropeptides can be released into thyroid blood vessels by electrical stimulation of the major thyroid nerves or whether their expression is altered by changes in iodine intake. Sprague-Dawley rats were used in this study. The cervical sympathetic trunk or the superior laryngeal nerve was stimulated by bipolar electrodes in anesthetized rats. During nerve stimulation, blood samples were withdrawn from the thyroid vein. Thyroid blood flow was monitored by laser Doppler blood flowmetry. Sympathetic stimulation caused a marked decrease in thyroid blood flow, which was associated with a significant increase in release of norepinephrine. However, these effects were not accompanied by any change in NPY release into the thyroid vein. Stimulation of the superior laryngeal nerve was not associated with changes in thyroid blood flow or VIP release into the thyroid vein. In a separate experiment, rats were fed a diet containing low-, high-, or normal iodine concentrations. Triiodothyronine (T3) and thyroxine (T4) levels in thyroid venous plasma were significantly reduced in rats fed a low-iodine diet but not in a separate group of rats fed a high iodine diet. However, these treatments had no effect on VIP or NPY concentrations in thyroid venous plasma or in thyroid ganglia. Thus, our results indicate that VIP and NPY, which are present in the thyroid nerves, may not be directly involved in the regulation of thyroid function.

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Biotransformation of Neuropeptides

Cited by 29 publications

References 57 publications

Many Peptides that Are Present in the External Zone of the Median Eminence Are Not Secreted into the Hypophysial Portal Blood of Sheep

Many Peptides that Are Present in the External Zone of the Median Eminence Are Not Secreted into the Hypophysial Portal Blood of Sheep

Study of Enteral versus Parenteral Application of the Gonadotropin Releasing Hormone Agonist Gonadorelin[6-D-Phe] (D-Phe6-LHRH) on LH Secretion in Goettinger Miniature Pigs

The Neuropeptides, VIP and NPY, That Are Present in the Thyroid Nerves Are Not Released into the Thyroid Vein

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