Abstract
1. Intravenous administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 150 micrograms kg-1) into conscious sham-operated rats caused significant increases in basal glycaemia with minor changes in basal insulinaemia. Glucose-stimulated (intravenous glucose tolerance test) plasma insulin levels were significantly inhibited in 8-OH-DPAT-treated sham-operated animals. These metabolic changes were associated with significant and sustained falls in blood pressure (BP) and heart rate (HR) preceded by transient (less than 5 min) increases only in BP. 2. In adrenodemedullated animals, 8-OH-DPAT failed to cause an initial vasoconstriction, hyperglycaemia, or inhibition of glucose-stimulated plasma insulin despite eliciting falls in BP and HR that were comparable to those observed in sham-operated animals. 3. Noradrenaline, adrenaline and dopamine levels in the adrenal tissue were reduced by about 95% in adrenodemedullated rats as compared to sham-operated rats. A functionally intact adrenal cortex was indicated by the presence of corticosterone in the plasma of both adrenodemedullated and sham-operated rats. 4. The present data demonstrate that 8-OH-DPAT mediates an initial increase in BP and changes in metabolic parameters via intact adrenal medulla and may thus be consequential to the release of adrenaline, whereas the sustained cardiovascular effects of 8-OH-DPAT are not.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahrén B., Taborsky G. J., Jr, Porte D., Jr Neuropeptidergic versus cholinergic and adrenergic regulation of islet hormone secretion. Diabetologia. 1986 Dec;29(12):827–836. doi: 10.1007/BF00870137. [DOI] [PubMed] [Google Scholar]
- Aulakh C. S., Wozniak K. M., Haas M., Hill J. L., Zohar J., Murphy D. L. Food intake, neuroendocrine and temperature effects of 8-OHDPAT in the rat. Eur J Pharmacol. 1988 Feb 9;146(2-3):253–259. doi: 10.1016/0014-2999(88)90300-7. [DOI] [PubMed] [Google Scholar]
- Bagdy G., Szemeredi K., Murphy D. L. Marked increases in plasma catecholamine concentrations precede hypotension and bradycardia caused by 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in conscious rats. J Pharm Pharmacol. 1989 Apr;41(4):270–272. doi: 10.1111/j.2042-7158.1989.tb06450.x. [DOI] [PubMed] [Google Scholar]
- Bouhelal R., Loubatières-Mariani M. M., Mir A. K. Investigation of the mechanism(s) of 8-OH-DPAT-mediated inhibition of plasma insulin in spontaneously hypertensive rats. Br J Pharmacol. 1990 May;100(1):173–179. doi: 10.1111/j.1476-5381.1990.tb12072.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bouhelal R., Mir A. K. Role of the adrenal gland in the metabolic and cardiovascular effects of 8-OH-DPAT in the rat. Eur J Pharmacol. 1990 May 31;181(1-2):89–95. doi: 10.1016/0014-2999(90)90248-5. [DOI] [PubMed] [Google Scholar]
- Brown M. R., Fisher L. A. Central nervous system effects of corticotropin releasing factor in the dog. Brain Res. 1983 Nov 28;280(1):75–79. doi: 10.1016/0006-8993(83)91175-7. [DOI] [PubMed] [Google Scholar]
- Brown M. R., Fisher L. A., Spiess J., Rivier C., Rivier J., Vale W. Corticotropin-releasing factor: actions on the sympathetic nervous system and metabolism. Endocrinology. 1982 Sep;111(3):928–931. doi: 10.1210/endo-111-3-928. [DOI] [PubMed] [Google Scholar]
- Brown M. R., Fisher L. A., Webb V., Vale W. W., Rivier J. E. Corticotropin-releasing factor: a physiologic regulator of adrenal epinephrine secretion. Brain Res. 1985 Mar 4;328(2):355–357. doi: 10.1016/0006-8993(85)91048-0. [DOI] [PubMed] [Google Scholar]
- Calogero A. E., Bernardini R., Margioris A. N., Bagdy G., Gallucci W. T., Munson P. J., Tamarkin L., Tomai T. P., Brady L., Gold P. W. Effects of serotonergic agonists and antagonists on corticotropin-releasing hormone secretion by explanted rat hypothalami. Peptides. 1989 Jan-Feb;10(1):189–200. doi: 10.1016/0196-9781(89)90096-x. [DOI] [PubMed] [Google Scholar]
- Chaouloff F., Baudrie V., Laude D. Evidence that 5-HT1A receptors are involved in the adrenaline-releasing effects of 8-OH-DPAT in the conscious rat. Naunyn Schmiedebergs Arch Pharmacol. 1990 Apr;341(4):381–384. doi: 10.1007/BF00180665. [DOI] [PubMed] [Google Scholar]
- Chaouloff F., Baudrie V., Laude D. Evidence that the 5-HT1A receptor agonists buspirone and ipsapirone activate adrenaline release in the conscious rat. Eur J Pharmacol. 1990 Feb 20;177(1-2):107–110. doi: 10.1016/0014-2999(90)90558-n. [DOI] [PubMed] [Google Scholar]
- Chaouloff F., Jeanrenaud B. 5-HT1A and alpha-2 adrenergic receptors mediate the hyperglycemic and hypoinsulinemic effects of 8-hydroxy-2-(di-n-propylamino)tetralin in the conscious rat. J Pharmacol Exp Ther. 1987 Dec;243(3):1159–1166. [PubMed] [Google Scholar]
- Chaouloff F., Jeanrenaud B. Hyperinsulinemia of the genetically obese (fa/fa) rat is decreased by a low dose of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Eur J Pharmacol. 1988 Feb 16;147(1):111–118. doi: 10.1016/0014-2999(88)90639-5. [DOI] [PubMed] [Google Scholar]
- Chaouloff F., Laude D., Baudrie V. Ganglionic transmission is a prerequisite for the adrenaline-releasing and hyperglycemic effects of 8-OH-DPAT. Eur J Pharmacol. 1990 Aug 21;185(1):11–18. doi: 10.1016/0014-2999(90)90205-k. [DOI] [PubMed] [Google Scholar]
- Doods H. N., Boddeke H. W., Kalkman H. O., Hoyer D., Mathy M. J., van Zwieten P. A. Central 5-HT1A receptors and the mechanism of the central hypotensive effect of (+)8-OH-DPAT, DP-5-CT, R28935, and urapidil. J Cardiovasc Pharmacol. 1988 Apr;11(4):432–437. doi: 10.1097/00005344-198804000-00008. [DOI] [PubMed] [Google Scholar]
- Fisher L. A. Corticotropin-releasing factor: endocrine and autonomic integration of responses to stress. Trends Pharmacol Sci. 1989 May;10(5):189–193. doi: 10.1016/0165-6147(89)90236-8. [DOI] [PubMed] [Google Scholar]
- Fozard J. R., Mir A. K., Middlemiss D. N. Cardiovascular response to 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis. J Cardiovasc Pharmacol. 1987 Mar;9(3):328–347. doi: 10.1097/00005344-198703000-00010. [DOI] [PubMed] [Google Scholar]
- Gradin K., Pettersson A., Hedner T., Persson B. Acute administration of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a selective 5-HT-receptor agonist, causes a biphasic blood pressure response and a bradycardia in the normotensive Sprague-Dawley rat and in the spontaneously hypertensive rat. J Neural Transm. 1985;62(3-4):305–319. doi: 10.1007/BF01252244. [DOI] [PubMed] [Google Scholar]
- HALES C. N., RANDLE P. J. Immunoassay of insulin with insulin-antibody precipitate. Biochem J. 1963 Jul;88:137–146. doi: 10.1042/bj0880137. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jones M. T., Hillhouse E. W., Burden J. Effect on various putative neurotransmitters on the secretion of corticotrophin-releasing hormone from the rat hypothalamus in vitro-a model of the neurotransmitters involved. J Endocrinol. 1976 Apr;69(1):1–10. doi: 10.1677/joe.0.0690001. [DOI] [PubMed] [Google Scholar]
- Kempf E., Mandel P. Reverse-phase high-performance liquid chromatographic separation and electrochemical detection of norepinephrine, dopamine, serotonin, and related major metabolites. Anal Biochem. 1981 Apr;112(2):223–231. doi: 10.1016/0003-2697(81)90285-2. [DOI] [PubMed] [Google Scholar]
- Koenig J. I., Gudelsky G. A., Meltzer H. Y. Stimulation of corticosterone and beta-endorphin secretion in the rat by selective 5-HT receptor subtype activation. Eur J Pharmacol. 1987 May 7;137(1):1–8. doi: 10.1016/0014-2999(87)90175-0. [DOI] [PubMed] [Google Scholar]
- Laude D., Baudrie V., Martin G. R., Chaouloff F. Effects of the 5-HT1 receptor agonists DP-5-CT, CGS 12066B, and RU 24969 on plasma adrenaline and glucose levels in the rat. Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):378–381. doi: 10.1007/BF00169452. [DOI] [PubMed] [Google Scholar]
- Le Floch J. P., Escuyer P., Baudin E., Baudon D., Perlemuter L. Blood glucose area under the curve. Methodological aspects. Diabetes Care. 1990 Feb;13(2):172–175. doi: 10.2337/diacare.13.2.172. [DOI] [PubMed] [Google Scholar]
- Ramage A. G., Fozard J. R. Evidence that the putative 5-HT1A receptor agonists, 8-OH-DPAT and ipsapirone, have a central hypotensive action that differs from that of clonidine in anaesthetised cats. Eur J Pharmacol. 1987 Jun 19;138(2):179–191. doi: 10.1016/0014-2999(87)90431-6. [DOI] [PubMed] [Google Scholar]
- Ramage A. G., Wouters W., Bevan P. Evidence that the novel antihypertensive agent, flesinoxan, causes differential sympathoinhibition and also increases vagal tone by a central action. Eur J Pharmacol. 1988 Jul 14;151(3):373–379. doi: 10.1016/0014-2999(88)90533-x. [DOI] [PubMed] [Google Scholar]
