Norepinephrine attenuates serotonin inhibition of pial venous tone.
Serotonin (5-hydroxytryptamine, 5-HT) has been shown to inhibit the rhythmic constrictions, accompanied by an increase in cAMP synthesis, in porcine pial veins. Since porcine pial veins contain predominant postsynaptic alpha 2-adrenoceptors which are coupled to Gi-protein, the possibility that the inhibitory effect of 5-HT is antagonized by norepinephrine was examined pharmacologically, using tissue bath techniques. The results indicated that norepinephrine (0.1-1 microM) attenuated 5-HT-induced inhibition of rhythmic constriction. This effect of norepinephrine was mimicked by clonidine (an alpha 2-adrenoceptor agonist), but not by methoxamine (an alpha 1-adrenoceptor agonist). Furthermore, the effect of norepinephrine was prevented by yohimbine (an alpha 2-adrenoceptor antagonist) and pertussis toxin, but was not prevented by prazosin (an alpha 1-adrenoceptor antagonist). In parallel studies, the basal concentration of cAMP and that induced by 5-HT in the pial veins were inhibited by norepinephrine (0.3 microM). These results are consistent with the previous findings that 5-HT-induced inhibition of rhythmic constriction in the porcine pial veins is associated with an increase in vascular cAMP synthesis and suggest that norepinephrine attenuates 5-HT-induced inhibition of rhythmic constriction in part by negatively coupling to adenylate cyclase via alpha 2-adrenoceptors.
Southern Illinois University School of Medicine, Department of Pharmacology, Springfield 62794-1222, USA.
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D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002550:Cerebral Veins / Q000187:drug effects* / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D037342:Pertussis Toxin; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013552:Swine; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014661:Vasoconstriction; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D011450:Prostaglandin Endoperoxides, Synthetic; D012702:Serotonin Antagonists; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D037342:Pertussis Toxin; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine