title: Centrally coinjected galanin and a 5-HT1A agonist act synergistically to produce vasodepressor responses in the rat.
abstract: The present study was undertaken to evaluate the possible functional implications of the previously demonstrated in vitro interactions between galanin and 5-HT1A receptors. To this end we analysed the interactions between galanin and the 5-HT1A receptor agonist 8-OH-2-(di-n-propylamino)-tetralin (8-OH-DPAT) in central cardiovascular regulation. 8-OH-DPAT given intracisternally (i.c.) produced a dose-dependent reduction of blood pressure, the peak action being 32% at 10 nmol of 8-OH-DPAT. Heart rate and respiration rate were not affected. The vasodepressor action of 8-OH-DPAT was counteracted by the 5-HT1A receptor antagonist 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190). A threshold dose (1 nmol) of galanin given i.c. was shown to enhance the vasodepressor effect of both an ED50 dose and a threshold dose of 8-OH-DPAT. Quantitative receptor autoradiography showed that the IC50 values for [125I]galanin binding sites were reduced in the presence of 8-OH-DPAT (10 nM) by approximately 40% in the dorsal region of the nucleus of the solitary tract, the area postrema, and the raphe pallidus and obscurus nuclei. Galanin (10 nM) also significantly increased the IC50 value for [3H]8-OH-DPAT binding sites within the nucleus of the solitary tract. The results provide evidence for a synergistic interaction between 8-OH-DPAT and galanin in cardiovascular regulation after their central administration, an interaction possibly related to the ability of 8-OH-DPAT to enhance the affinity of the galanin receptor within regions of the medulla oblongata involved in cardiovascular control.
authors.affiliation: Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P B
authors.initials: PB
authors.lastname: Hedlund
authors.forename: J A
authors.initials: JA
authors.lastname: Aguirre
authors.forename: J A
authors.initials: JA
authors.lastname: Narvaez
authors.forename: K
authors.initials: K
authors.lastname: Fuxe
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D019004:Galanin; D008297:Male; D008526:Medulla Oblongata / Q000648:ultrastructure; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism; D011985:Receptors, Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019004:Galanin