Centrally coinjected galanin and a 5-HT1A agonist act synergistically to produce vasodepressor responses in the rat.
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.
Hedlund
P B
PB
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Aguirre
J A
JA
Narvaez
J A
JA
Fuxe
K
K
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*
D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019004:Galanin