Effects of pituitary beta-endorphin secretagogues on the concentration of beta-endorphin in rat cerebrospinal fluid: evidence for a role of vasopressin in the regulation of brain beta-endorphin release.
The concentration of beta-endorphin-immunoreactivity (beta E-IR) in cerebrospinal fluid (CSF) and plasma of rats was determined following intracerebroventricular (ICV) treatment of conscious animals with substances known to stimulate the release of beta E and other pro-opiomelanocortin (POMC)-derived peptides at the level of the anterior and intermediate lobes of the pituitary. The beta-adrenoceptor agoinst isoproterenol (ISO) did not influence the concentration of beta E-IR in CSF collected 5-60 min after ICV administration of doses ranging from 3 to 30,000 pg/rat. Plasma beta E-IR levels, however, were significantly increased 20 min following ICV injection of 30,000 pg ISO. ICV treatment of animals with ovine corticotropin-releasing factor (CRF; 30-30,000 pg/rat) also did not affect CSF levels of beta E-IR, whereas CRF in a dose of 30 pg significantly decreased, and in doses of 300-30,000 pg enhanced plasma beta E-IR concentrations as determined by 20 min following treatments. ICV injection of arginine8-vasopressin (AVP) in doses of 10-1,000 pg/rat dose-dependently elevated the beta E-IR concentration in CSF without affecting plasma beta E-IR levels. This AVP-induced increase in CSF beta E-IR was maximal 20-35 min and beta E-IR levels had returned to basal 60 min following treatment. The data indicate that AVP and not ISO and CRF is a stimulator of CSF levels of beta E-IR. As beta E-IR in CSF likely originates from brain POMC neurons, these results suggest the hot vasopressin may be a physiological regulator of brain POMC activity, and may act as a releasing factor for POMC-derived peptides in the brain.
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Rudolf Magnus Institute, Department of Pharmacology, Medical Faculty, University of Utrecht, The Netherlands.
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Veldhuis
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Wiegant
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De Wied
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D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000502:physiology*; D001921:Brain / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000502:physiology*; D007276:Injections, Intraventricular; D007545:Isoproterenol / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010902:Pituitary Gland / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000097:blood / Q000134:cerebrospinal fluid*
D001127:Arginine Vasopressin; D001615:beta-Endorphin; D003346:Corticotropin-Releasing Hormone; D007545:Isoproterenol