Differential effects of electrical stimulation, blockade of neuronal amine uptake and activation of alpha 2-adrenoceptors on the release of endogenous noradrenaline and 5-hydroxytryptamine from the isolated rat pineal gland.
Isolated rat pineal glands were incubated in vitro and the release of endogenous noradrenaline or 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was determined by HPLC with electrochemical detection. In the absence of test drugs, the spontaneous outflow of noradrenaline was about 10 fmol/10 min and electrical stimulation (5 Hz, 1500 pulses) evoked the release of about 70 fmol noradrenaline. Nomifensine enhanced the spontaneous outflow of noradrenaline about threefold and the electrically evoked release of noradrenaline about sixfold. In the presence of nomifensine, the alpha 2-adrenoceptor antagonist yohimbine markedly increased the electrically evoked release of noradrenaline, whereas the alpha 1-adrenoceptor antagonist prazosin had no effect. Clonidine inhibited the electrically evoked release of noradrenaline by about 65%, and this was antagonized by yohimbine in a competitive manner. In the absence of drugs, the initial spontaneous outflow of 5-HT was (compared with noradrenaline) very high 64 pmol/10 min). It declined by 80% within 1 h of incubation in vitro. The outflow of 5-HIAA amounted initially to 38 pmol 10 min and declined by 40% within 1 h of incubation. Addition of L-tryptophan (10 mumol/l) after 1 h of incubation in vitro largely enhanced the outflow of 5-HT and 5-HIAA within 30 min of incubation (about ten- and fourfold, respectively). When L-tryptophan was present from the onset of incubation the initial outflow of 5-HT and 5-HIAA was only slightly elevated, but the decline was largely attenuated. Neither omission of calcium nor addition of nomifensine, clonidine or yohimbine significantly affected the spontaneous outflow of 5-HT or 5-HIAA.(ABSTRACT TRUNCATED AT 250 WORDS)
Racké
K
K
Pharmakologisches Institut, Universität Mainz, Federal Republic of Germany.
Sommer
M
M
Burns
F
F
Hering
B
B
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004558:Electric Stimulation; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D014364:Tryptophan / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D011942:Receptors, Adrenergic, alpha; D009627:Nomifensine; D015016:Yohimbine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D009638:Norepinephrine