title: Effect of p-chlorophenylalanine on release of 5-hydroxytryptamine from the rat frontal cortex in vivo.
abstract: 1. Rats were given p-chlorophenylalanine (PCPA, 150 mg kg-1, i.p.) to inhibit partially 5-hydroxytryptamine (5-HT) synthesis so that its concentration in the frontal cortex fell by about half. The effects of this treatment on frontal cortex dialysate 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined before and after stimulation by increasing K+ concentration in the perfusion fluid by 100 mM for 20 min. Rates of 5-HT synthesis as indicated by the effects of 3-hydroxybenzylhydrazine (NSD 1015, 150 mg kg-1, i.p.) on frontal cortex tissue and dialysate 5-hydroxytryptophan (5-HTP) and dialysate 5-HIAA were also measured in rats that had not been stimulated with K+. 2. Dialysate 5-HT and 5-HIAA concentrations of both vehicle- and PCPA-treated rats fell into major (group 1) and minor (group 2) populations statistically distinguishable from each other by the high 5-HT and low 5-HIAA values of the latter group. 3. In group 1 animals, PCPA decreased both the dialysate 5-HT concentration and its rise following stimulation by K+ in proportion with the decrease of 5-HT in frontal cortex tissue. 5-HIAA fell more markedly than 5-HT and in similar proportion in both tissue and dialysate. The fall of dialysate 5-HIAA on stimulation by K+ was also attenuated to the same degree. The elevated 5-HT/5-HIAA ratios after PCPA treatment imply increased conservation of the depleted 5-HT stores. 4. PCPA decreased the above 5-HIAA values and the effects of NSD 1015 on tissue 5-HTP or dialysate 5-HIAA concentrations in similar proportion. However, PCPA had little effect on corresponding dialysate 5-HTP values. 5. The results are discussed with respect to relationships between synthesis, storage and release of 5-HT. They indicate that (under the conditions of the present study) the availability of 5-HT to receptors is directly proportional to total vesicular stores under both basal conditions and during neuronal firing.
authors.affiliation: Department of Neurochemistry, Institute of Neurology, London.
authors.forename: M T
authors.initials: MT
authors.lastname: O'Connell
authors.forename: C M
authors.initials: CM
authors.lastname: Portas
authors.forename: G S
authors.initials: GS
authors.lastname: Sarna
authors.forename: G
authors.initials: G
authors.lastname: Curzon
mesh_terms: D006916:5-Hydroxytryptophan / Q000032:analysis / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003956:Dialysis; D004563:Electrochemistry; D010134:Fenclonine / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000032:analysis / Q000378:metabolism; D008297:Male; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
chemical_list: D006834:Hydrazines; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; C004297:3-hydroxybenzylhydrazine; D006916:5-Hydroxytryptophan; D010134:Fenclonine; D011188:Potassium