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İntraserebroventriküler Olarak Uygulanan Exendin-(9-39) Santral “Glucagon-Like Peptide-1”in Kardiyovasküler Etkilerini Önler mi?

Does Intracerebroventricularly-Injected Exendin-(9-39) Prevent the Cardiovascular Effects of Central Glucagon-Like Peptide-1?

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Abstract (2. Language): 
In this study, we aimed to investigate the effects of intracerebroventricularly (i.c.v.)-injected glucagon-like peptide-1 (GLP-1) on blood pressures and heart rates of conscious, freely-moving rats, and whether specific receptors mediate these effects. Male Wistar albino rats used throughout the experiments were implanted with a cathether through the right femoral artery and with a cannula into the right lateral ventricle for i.c.v. injections, under ether anesthesia. Blood pressure and heart rate were recorded by a “TDA96 Transducer Data Acquisition System”. Blood pressures and heart rates of rats were observed before and for 30 minutes following drug injections. I.c.v. GLP-1 (100, 500 and 1000 ng/10 µl) caused a dose-dependent increase in both blood pressure and heart rate. The effects of GLP-1 on blood pressure and heart rate were inhibited by i.c.v. receptor antagonist exendin-(9-39) (2500 ng/µl). Our data indicate that i.c.v. GLP-1 increases blood pressure and heart rate, and that activation of central specific receptors mediate these effects.
Abstract (Original Language): 
Bu çalışmada uyanık, serbestçe hareket edebilen sıçanlara intraserebroventriküler (i.c.v.) olarak enjekte edilen “glucagon-like peptide-1” (GLP-1)’in kan basıncı ve kalp hızı üzerine olan etkileri ve bu etkilerine santral spesifik reseptörlerinin aracılık edip etmediğinin belirlenmesi amaçlandı. Deneylerde kullanılan erkek Wistar albino sıçanlara eter anestezisi altında, sağ femoral artere kateter ve i.c.v. enjeksiyonlar için sağ lateral ventriküle kanül yerleştirildi. Arteriyel kan basıncı ve kalp hızı, “TDA96 Transducer Data Acquisition System” aracılı- ğıyla kaydedildi. Sıçanların ilaç enjeksiyonlarından önce ve enjeksiyonları takiben 30 dakika süresince kan basınçları ve kalp hızları kaydedildi. İ.c.v. yolla verilen GLP-1 (100, 500 ve 1000 ng/10µl) kan basıncı ve kalp hızında doza bağlı olarak artış oluşturdu. GLP-1’in bu etkilerini i.c.v. olarak enjekte edilen reseptör antagonisti exendin-(9-39) (2500ng/10µl) inhibe etti. Bulgularımız i.c.v. GLP-1’in kan basıncı ve kalp hızını yükselttiğini, bu etkilerine santral spesifik reseptörlerinin aracılık ettiğini göstermektedir.
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REFERENCES

References: 

1. Fehmann HC, Habener JF. Insulinotropic glucagon-like
peptide-1 (7-37)/(7-36) amide: a new incretin hormone.
Trends Endocrinol Metab 1992;3:158-63.
2. Mojsov S, Heinrich G, Wilson IB, et al. Preproglucagon gene
expression in pancreas and intestine diversifies at the level of
post-translational processing. J Biol Chem 1986;261:11880-9.
3. Jin SL, Han VKM, Simmons JG, et al. Distribution of
glucagon-like peptide-1 (GLP-1), glucagon, and glisentin in
the rat brain: an immunocytochemical study. J Comp Neurol
1988;271:519-32.
4. Kreymann B, Ghatei MA, Burnet P, et al. Characterisation of
glucagon-like peptide-1 (7-36) amide in the rat hypothalamus.
Brain Res 1989;502:325-31.
5. Elliot RM, Morgan LM, Tredger S, et al. Glucagon-like
peptide-1 (7-36) amide and glucose-dependent insulinotropic
polypeptide secretion in response to nutrient ingestion in man:
acute post-prandial and 24-h patterns. J Endocrinol
1993;138:159-66.
6. Wei Y, Mojsov S. Tissue-specific expression of the human
receptor for glucagon-like peptide-1: brain, heart and
pancreatic forms have the same deduced amino acid
sequences. FEBS Lett 1995;358:219-24.
7. Edwards CMB, Edwards AV, Bloom R. Cardiovascular and
pancreatic endocrine responses to glucagon-like peptide-1-(7-
36) amide in the conscious calf. Exp Physiol 1997;82:709-16.
8. Edwards CMB, Todd JF, Ghatei MA. Subcutaneous glucagonlike peptide-I (7-36) amide is insulinotropic and can cause
hypoglycaemia in fasted healthy subjects. Clin Sci
1998;96:719-24.
9. O’Halloran DJ, Nikou GC, Kreymann B, et al. Glucagon-like
peptide-1 (7-36)-NH2: a physiological inhibitor of gastric acid
secretion in man. J Endocrinol 1990;126:169-73.
10. Wettergren A, Wqjdemann M, Holst JJ. Glucagon-like
peptide-1 inhibits gastropancreatic function by inhibiting
central parasympathetic outflow. Am J Physiol (Gastrointest
Liver Physiol) 1998;275(38):984-92.
11. Barragan JM, Rodriguez RE, Blazquez E. Changes in arterial
blood pressure and heart rate induced by glucagon-like
peptide-1-(7-36) amide in rats. Am J Physiol (Endocrinol
Metab) 1994;266 (29):456-66.
12. Barragan JM, Rodriguez RE, Eng J, Blazquez E. Interaction of
exendin-(9-39) with the effects of glucagon-like peptide-1-(7-
36) amide and of exendin-4 on arterial blood pressure and
heart rate in rats. Regul Pept 1996;67:63-8.
13. Barragan JM, Eng J, Rodriguez R, Blazquez E. Neural
contribution to the effect of glucagon-like peptide-1-(7-36)
amide on arterial blood pressure in rats. Am J Physiol
(Endocrinol Metab) 1999;277 (40):784-91.
14. Bojanovska E, Stempniak B. Effects of centrally or
systemically injected glucagon-like peptide-1-(7-36) amide on
release of neurohypophysial hormones and blood pressure in
the rat. Regul Pept 2000;91:75-81.
15. Göke R, Fehmann HC, Linn T, et al. Exendin-4 is a high
potency agonist and truncated exendin-(9-39)-amide an
antagonist at the glucagon-like peptide 1-(7-36)-amide
receptor of insulin-secreting β-cells. J Biol Chem
1993;268(26):19650-5.
16. Kollgs F, Fehmann HC, Göke R, Göke B. Reduction of the
incretin effect in rats by the glucagon-like peptide 1 receptor
antagonist exendin (9-39) amide. Diabetes 1995;44(1):16-9.
17. Cancelas J, Villanueva-Penacarrillo ML, Valverde I, Malaisse
WJ. Supression by exendin(9-39) amide of glucagon-like
peptide-1 insulinotropic action in rats infused with dimethyl
ester of succinic acid. Endocrine 2001;15(3):283-5.
18. Daniel EE, Anvari M, Fox-Threlkeld JE, McDonald TJ. Local,
exendin-(9-39)-insensitive, site of action of GLP-1 in canine
ileum. Am J Physiol (Gastrointest Liver Physiol)
2002;283(3):595-602.
19. Eng J, Kleiman WA, Singh L, et al. Isolation and
characterization of exendin-4, and exendin-3 analogue, from
Heloderma suspectum venom. Further evidence for an
exendin receptor on dispersed acini from guinea pig pancreas.
J Biol Chem 1992;267:7402-5.
20. Bullock BP, Heller RS, Habener JF. Tissue distribution of
messenger ribonucleic acid encoding the rat glucagon-like
peptide-1 receptor. Endocrinology 1996;137:2968-78.
21. Merchenthaler I, Lane M, Shughrue P. Distribution of pre-proglucagon and glucagon-like peptide-1 receptor messenger
RNAs in the rat central nervous system. J Comp Neurol
1999;403:261-80.
22. Goke R, Larsen PJ, Mikkelsen JD, Sheikh SP. Distribution of
GLP-1 binding sites in the rat brain: evidence that exendin-4
is a ligand of brain GLP-1 binding sites. Eur J Neurosci
1995;7:2294-300.
23. Yamamoto H, Kishi T, Lee CE, et al. Glucagon-like peptide-1
responsive catecholamine neurons in the area postrema link
peripheral glucagon-like peptid-1 with central autonomic
control sites. J Neurosci 2003;23(7):2939-46.
24. Turton MD, O’Shea DO, Gunn I, et al. A role for glucagonlike peptide-1 in the central regulation of feeding. Nature
1996;379:69-72.
25. Meeran K, O’Shea D, Edwards CM, et al. Repeated
intracerebroventricular administration of glucagon-like
peptide-1-(7-36) amide or exendin-(9-39) alters body weight
in the rat. Endocrinology 1999;140:244-50.
26. Yamamoto H, Lee CH, Marcus JN, et al. Glucagon-like
peptide-1 receptor stimulation increases blood pressure and
heart rate and activates autonomic regulatory neurons. J Clin
Invest 2002;110:43-52.
27. Bachelard H, Gardiner SM, Bennett T. Cardiovascular
responses elicited by chemical stimulation of the rostral
ventrolateral medulla in conscious, unrestrained rats. J Auton
Nerv Syst 1990;31:185-90.

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