title: Neuroleptic Drugs and PACAP Differentially Affect the mRNA Expression of Genes Encoding PAC1/VPAC Type Receptors.
abstract: Several lines of evidence suggest that pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide playing an important role as a neuromodulator. It has been indicated that PACAP is associated with mental diseases, and that regulation of the PACAPergic signals could be a potential target for the treatment of such psychiatric states as schizophrenia. Recent studies have suggested that action of neuroleptic drugs is mediated not only by dopaminergic and serotonergic neurotransmission, but also via neuropeptides which may act both as neurotransmitters and as neuromodulators. The present study examines whether currently-used neuroleptics influence the action of PACAP receptors, whose expression is altered in a schizophrenic patient. Real-time polymerase chain reaction (PCR) was used to examine the effects of haloperidol, olanzapine and amisulpride on the expression of genes coding PAC1/VPAC type receptors in the T98G glioblastoma cell line, as an example of an in vitro model of glial cells. PAC1 mRNA expression fell after 24-h incubation with haloperidol or olanzapine; however the effect was not maintained after 72 h, and haloperidol even up-regulated PAC1 mRNA expression in a dose-dependent manner. All the examined drugs decreased VPAC2 mRNA expression, especially after 72-h incubation. Haloperidol (typical neuroleptic) was distinctly more potent than atypical neuroleptic drugs (olanzapine and amisulpride). In addition, PACAP increased PAC1 and VPAC2 mRNA expression. In conclusion, our findings suggest PACAP receptors may be involved in the mechanism of typical and atypical neuroleptic drugs.
authors.affiliation: Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology and Toxicology, Medical University of Lodz, Zeligowskiego 7/9, 90-752, Lodz, Poland. marta.jozwiak-bebenista@umed.lodz.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Jóźwiak-Bębenista
authors.affiliation: Department of Pharmacology and Toxicology, The Interfaculty Chair of Basic and Clinical Pharmacology and Toxicology, Medical University of Lodz, Zeligowskiego 7/9, 90-752, Lodz, Poland.
authors.forename: Edward
authors.initials: E
authors.lastname: Kowalczyk
mesh_terms: D014150:Antipsychotic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006801:Humans; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000096:biosynthesis* / Q000235:genetics; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C495401:ADCYAP1 protein, human; D014150:Antipsychotic Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I
keywords: Glioma cell line T98G; Neuroleptic drugs; Neuropeptides; PAC1; PACAP; VPAC2