Effects of xylamine on vascular neuroeffector transmission.
The effect of xylamine on sympathetic neuroeffector transmission in rabbit isolated blood vessels was examined. Xylamine (10(-8) to 10(-6) M) caused a slowly progressing inhibition of the contractions of pulmonary artery evoked by electrical field stimulation. The inhibition was irreversible. Cocaine (3 x 10(-5) M) prevented the inhibitory action of xylamine (10(-7) M), but it did not reverse the inhibition caused by xylamine (10(-6) M). Xylamine (10(-7) to 3 x 10(-5) M) reduced the accumulation of [3H]norepinephrine (NE) (10(-8) M). In the presence of desipramine (10(-6) M), xylamine (10(-7) to 3 x 10(-5) M) and corticosterone (10(-6) to 10(-4)) reduced the 3H-accumulation. Xylamine (10(-7) to 10(-5) M) reduced the tissue NE content by up to 50%. Xylamine (10(-7) to 10(-6) M) antagonized in a noncompetitive manner the contractions of aorta evoked by NE (10(-9) to 3 x 10(-5) M), histamine (10(-6) to 3 x 10(-4) M) and 5-hydroxytryptamine (10(-8) to 3 x 10(-4) M). In the case of NE, the antagonism was more marked in the presence of either cocaine (3 x 10(-5) M) plus corticosterone (4 x 10(-5) M) or corticosterone (4 x 10(-5) M). In the presence of xylamine (10(-7) to 10(-6) M), cumulative addition of near maximally effective concentrations of NE, 5-hydroxytryptamine and histamine caused a progressive and complete relaxation of aorta. Xylamine (10(-7) to 10(-5) M) did not alter the contractions of aorta evoked by potassium (17-55 mM). The results support the contention that xylamine is an inhibitor of neuronal and extraneuronal uptake, an adrenergic neurone blocking agent and a noncompetitive antagonist of alpha-1 adrenoceptors, histamine and 5-hydroxytryptamine2 receptors. Xylamine is not a direct acting vasodilator on smooth muscle.
Nedergaard
O A
OA
Department of Pharmacology, School of Medicine, Odense University, Denmark.
Cho
A K
AK
Waggaman
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LA
D000818:Animals; D003042:Cocaine / Q000494:pharmacology; D004347:Drug Interactions; D004558:Electric Stimulation; D006632:Histamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009451:Neuroeffector Junction / Q000187:drug effects; D009588:Nitrogen Mustard Compounds / Q000494:pharmacology*; D009638:Norepinephrine / Q000378:metabolism*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology*
D009588:Nitrogen Mustard Compounds; D013566:Sympathomimetics; D012701:Serotonin; C026131:xylamine; D006632:Histamine; D003042:Cocaine; D009638:Norepinephrine