title: Interaction of BKCa channel modulators with adrenergic agonists in the rat aorta is influenced by receptor reserve.
abstract: Our main objective was to study the interaction of BKCa channel modulators with adrenergic agonists UK 14304 and noradrenaline (NA), acting on alpha1-adrenoceptors, in the rat aorta and how this is affected by receptor reserve. NA and UK 14304 evoked concentration-dependent contractions of the rat aorta. UK 14304 was a partial agonist relative to NA in this preparation. The BK(Ca) channel blocker tetraethylammonium (TEA, 1 mM) and opener NS 1619 (3 x 10(-5) M) modulated NA- and UK 14304-induced contractions, and were more effective on UK 14304-induced contractions. TEA (1 mM) increased the maximum response to NA and UK 14304 by about 13% and 300%, respectively, while NS 1619 (3 x 10(-5) M) reduced the maximum response to UK 14304 by about 81% compared to 31% for noradrenaline. The effect of TEA on the noradrenaline concentration-response curve was increased after treatment of the aorta with phenoxybenzamine (PBZ), an irreversible alpha1-adrenoceptor antagonist, to reduce receptor reserve. We concluded that the interaction of BKCa channel modulators with alpha1-adrenergic agonists in the rat aorta was influenced by receptor reserve.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait.
authors.forename: Hanadi
authors.initials: H
authors.lastname: El-Hajj
authors.forename: Bindu
authors.initials: B
authors.lastname: Chandrasekhar
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Kadavil
authors.forename: Mabayoje A
authors.initials: MA
authors.lastname: Oriowo
mesh_terms: D000322:Adrenergic Agonists / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D011921:Rats, Inbred WKY; D011941:Receptors, Adrenergic / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology
chemical_list: D000322:Adrenergic Agonists; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D015221:Potassium Channels; D011941:Receptors, Adrenergic; D009638:Norepinephrine