Abstract
There are some suggestions that, in the pineal gland, serotonin acts not only as a precursor of melatonin but also plays a role in the modulation of the pineal biosynthetic activity. To corroborate this possible neuromodulatory role of 5-hydroxytryptamine (serotonin) (5-HT) on the pineal gland, the effects of two 5-HT2 receptor agonists meta-chlorophenylpiperazine (m-CPP) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane were assessed in vivo on pineal N-acetyltransferase (NAT) activity and melatonin content in rats. m-CPP potentiated the enhancement of NAT activity and pineal melatonin content induced by isoproterenol administration during daytime, whereas it did not affect the diurnal basal biosynthetic activity of the gland. At night,m-CPP and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane enhanced significantly the physiological increases in both pineal NAT activity and melatonin content. This enhancement was prevented by pretreatment withN-(1-methyl-5-indolyl)-N′-(3-pyridyl) urea hydrochloride, an antagonist with higher affinity for 5-HT2B/C than for 5-HT2A receptor, as well as by pretreatment with 8-[5-(2,4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-oxopenthyl]-1,3,8-triazospiro[4,5]decane-2,4-dione, the most specific 5-HT2C receptor now available, but not by pretreatment with ketanserin, an antagonist with higher affinity for 5-HT2A than for 5-HT2C receptor. These results suggest that 5-HT2C receptors are likely involved in the mediation of the serotonergic modulation of pineal biosynthetic activity in rats.
Footnotes
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Send reprint requests to: Luca Steardo, M.D., Istituto di Farmacologia, Università di Palermo, Via Forlanini 1, 90134 Palermo, Italy. E-mail: monteri{at}tin.it
- Abbreviations:
- NE
- norepinephrine
- 5-HT
- 5-hydroxytryptamine (serotonin)
- NAT
- N-acetyl transferase
- m-CPP
- meta-chlorophenylpiperazine
- DOI
- 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane
- KET
- ketanserine
- SB 200646A
- N-(1-methyl-5-indolyl)-N′-(3-pyridyl) urea hydrochloride
- RS 102221
- 8-[5-(2,4-dimethoxy-5-(4-trifluoromethyl-phenylsulphonamido)-phenyl-5-oxopenthyl]-1,3,8-triazospiro[4,5]decane-2,4-dione
- DMSO
- dimethyl sulfoxide
- Received April 19, 2000.
- Accepted June 30, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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