Effects of nanomolar to submillimolar carteolol on noradrenaline release in the absence and presence of uptake1 and uptake2 blockers in guinea pig pulmonary arteries.
Effects of nanomolar to submillimolar carteolol, a non-selective beta-antagonist, on the evoked release at 1 Hz and the spontaneous release in the absence and presence of uptake1 and uptake2 blockers were studied in pulmonary arteries, isolated from guinea pigs, and then preloaded with [3H]noradrenaline. dl-Carteolol at 10(-8), 10(-7) and 10(-6) M applied at the increasing concentrations inhibited the evoked [3H]-release in untreated arteries and in desipramine and corticosterone-treated arteries. The spontaneous [3H]-release slightly but significantly increased or tended to increase in untreated arteries. dl-Carteolol at 10(-5) and 10(-4) M clearly and concentration-dependently increased the spontaneous [3H]-release in untreated and cocaine-treated arteries. This increase was markedly inhibited by further pretreatment with normetanephrine. The evoked [3H]-release was not altered by dl-carteolol at 10(-5) M, but increased at 10(-4) M. This increase was not modified by cocaine and by cocaine and normetanephrine. d-Carteolol at 10(-5) and 10(-4) M produced effects similar to those of dl-carteolol. Nanomolar to micromolar dl-carteolol inhibits the evoked [3H]-release, which supports our previous conclusion that this inhibition is due to blockade of tonically functioning presynaptic beta 2-adrenoceptors. Carteolol at the higher concentrations seems to become a substrate for an uptake2 mechanism and to produce an unknown sympathomimetic activity in guinea pig pulmonary arteries.
Matsushita
N
N
Department of Pharmacology, Yokohama City University School of Medicine, Japan.
Kuwahara
M
M
Goshima
Y
Y
Misu
Y
Y
D000818:Animals; D002354:Carteolol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004347:Drug Interactions; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009638:Norepinephrine / Q000378:metabolism*; D009647:Normetanephrine / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism
D009647:Normetanephrine; D002354:Carteolol; D003042:Cocaine; D003891:Desipramine; D003345:Corticosterone; D009638:Norepinephrine