Effects of 6-hydroxydopamine on pre- and post-junctional 5-HT1-like receptor-mediated responses in dog saphenous vein

• Published in: Naunyn-Schmiedeberg's archives of pharmacology 1993-03, Vol.347 (3), p.257-265
• Main Authors: MEDHURST, A. D, NOVOTNY, G. E. K, PARKER, S. G, DEIGHTON, N. M, KAUMANN, A. J
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Blood vessels and receptors; Cyclic AMP - metabolism; Dogs; Female; Fundamental and applied biological sciences. Psychology; In Vitro Techniques; Male; Microscopy; Microscopy, Electron; Neuroeffector Junction - drug effects; Neuroeffector Junction - metabolism; Norepinephrine - metabolism; Oxidopamine - pharmacology; Potassium - pharmacology; Receptors, Serotonin - drug effects; Receptors, Serotonin - physiology; Saphenous Vein - drug effects; Saphenous Vein - innervation; Serotonin - pharmacology; Vasoconstriction - drug effects; Vertebrates: cardiovascular system
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/BF00167443

To investigate whether 5-HT1-like receptor-mediated inhibition of adenosine 3':5'-cyclic monophosphate (cyclic AMP) accumulation occurs in nerves or smooth muscle of saphenous vein, infusions of 6-hydroxydopamine (6-OHDA) were administered to dogs with the aim of inducing sympathetic nerve damage. The effects of 6-OHDA on other 5-HT1-like receptor-mediated responses at the pre- and post-junctional level were investigated for comparison by studying 5-hydroxytryptamine (5-HT)-induced inhibition of 3H-noradrenaline release and contraction of smooth muscle respectively. Disruption of nerve function by 6-OHDA was revealed by the lack of catecholaminergic fluorescence and neurogenic contractile responses in saphenous veins from dogs treated with 6-OHDA. In addition, severe impairment of neuronal uptake mechanisms were apparent since basal efflux of 3H-noradrenaline, electrically-evoked release of 3H-noradrenaline and remaining 3H-noradrenaline content were considerably reduced. Some 3H-noradrenaline was taken up and released in 6-OHDA-treated tissues which is consistent with the existence of nerve varicosities resistant to the present dosing regime of 6-OHDA, an observation substantiated by electron microscopy studies showing inconsistent lesions of nerve terminals. 6-OHDA pre-treatment potentiated the smooth muscle contractile responses mediated by 5-HT1-like receptors as well as potentiating 5-HT-evoked inhibition of prostaglandin E2-stimulated cyclic AMP accumulation. It did not, however, affect 5-HT-induced inhibition of 3H-noradrenaline release. The present results suggest that inhibition of cyclic AMP accumulation by 5-HT occurs predominantly in smooth muscle.