Effect of ouabain on the rabbit ear artery contraction to serotonin: enhanced response mediated by serotonergic rather than alpha adrenergic receptors.
The effect of ouabain on the rabbit ear artery response to serotonin was assessed in isolated vascular rings mounted in tissue baths for the measurement of isometric contractions and denervated with 6-hydroxydopamine in vitro. Ouabain, 1 and 10 microM, caused 5- and 6-fold shifts to the left of the serotonin concentration-response curve (CRC). However, 10 microM ouabain caused only a 1.6-fold shift to the left of the norepinephrine CRC. In the absence of ouabain, 0.01 microM ketanserin had little effect, whereas 0.1 microM prazosin caused a marked shift to the right of the serotonin CRC. In the presence of ouabain, prazosin exhibited little or no antagonism below 3 microM serotonin. Antagonism by ketanserin was increased by 1 and 10 microM ouabain, yielding 6.5- and 10.5-fold shifts to the right of the serotonin CRC, respectively. Benextramine pretreatment to inactivate alpha adrenoceptors nearly abolished the rabbit ear artery response to serotonin. However, in the presence of 10 microM ouabain, there was a substantial recovery of the response to serotonin, and this response was antagonized by ketanserin. These results are consistent with our hypothesis that serotonergic receptors are present in the smooth muscle cell membranes of the rabbit ear artery but are either uncoupled to the contractile mechanism or in a low efficacy state. In the presence of ouabain, these receptors either become coupled or convert to a high efficacy state and thereby contribute to the serotonin-induced contraction. Because the serotonin CRC was shifted to the left in the presence of ouabain, it is likely that most of the CRC was below the threshold concentration at which serotonin activates alpha adrenoceptors. Thus antagonism by prazosin was lost.
Xu
Z
Z
Department of Pharmacology, Guandong Medical and Pharmaceutical College, Guangzhou, People's Republic of China.
Mondal
G
G
Song
J P
JP
Purdy
R E
RE
D000818:Animals; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D016627:Oxidopamine; D011224:Prazosin / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D006892:Hydroxydopamines; D011942:Receptors, Adrenergic, alpha; D011985:Receptors, Serotonin; D012701:Serotonin; D010042:Ouabain; D016627:Oxidopamine; D009638:Norepinephrine; D011224:Prazosin