0000000000524874
AUTHOR
Yolanda Madrero
Characterization of two different Ca2+ entry pathways dependent on depletion of internal Ca2+ pools in rat aorta
Ryanodine (10 microM), thapsigargin (1 microM) and cyclopiazonic acid (10 microM) produced a slow, sustained contractile response in rat aorta that only can be observed in Ca2+-containing solution. In Ca2+-free medium, no response to the drugs was obtained, which suggests that the contraction elicited in presence of Ca2+ is mainly due to the contribution of extracellular influx. This Ca2+ entry does not depend on the opening of dihydropyridine-dependent Ca2+-channels for nimodipine does not affect this. Noradrenaline (1 microM) induced a biphasic response in Ca2+-free medium that was mediated by two different Ca2+ compartments, one of which is common to caffeine (10 mM), and is also deplete…
Halogenated derivatives of boldine with high selectivity for alpha1A-adrenoceptors in rat cerebral cortex.
The selectivity of 3-nitrosoboldine and different halogenated derivatives of boldine (3-bromoboldine, 3,8-dibromoboldine and 3-chloroboldine) for alpha1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. In the competition experiments [3H]-prazosin binding was inhibited completely by all the compounds tested. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components. The relative order of affinity and selectivity for alpha1A-adrenoceptors was 3-bromoboldine = 3,8-dibromoboldine = 3-chloroboldineboldine3-nitrosoboldine. The competition curves for 3-bromoboldine remained shallow and biph…
Functional characterization of α1 -adrenoceptor subtypes in vascular tissues using different experimental approaches:a comparative study
The α1-adrenergic responses of rat aorta and tail artery have been analysed measuring the contractility and the inositol phosphate (IP) formation induced by noradrenaline. Three antagonists, prazosin, 5-methylurapidil (α1A selective) and BMY 7378 (α1D selective) have been used in different experimental procedures. Noradrenaline possesses a greater potency inducing contraction and IP accumulation in aorta (pEC50-contraction=7.32±0.04; pEC50-IPs=6.03±0.08) than in the tail artery (pEC50-contraction=5.71±0.07; pEC50-IPs=5.51±0.10). Although the maximum contraction was similar in both tissues (Emax-tail=619.1±55.6 mg; Emax-aorta-698.2±40.8 mg), there were marked differences in the ability of th…
8-NH2-Boldine, an Antagonist of α1Aand α1BAdrenoceptors without Affinity for the α1DSubtype: Structural Requirements for Aporphines at α1-Adrenoceptor Subtypes
Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human alpha (1A), alpha (1B) and alpha (1D) adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each alpha (1)-AR subtype. All the compounds tested competed for [ (125)I]-HEAT binding with steep and monophasic curves. The most interesting compound was 8-NH (2)-boldine, which retains the selective affinity for alpha(1A)-AR (pKi = 6.37 +/- 0.21) vs. alpha(1B)-AR (pKi = 5.53 +/- 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for alpha(1D)-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cor…
A possible structural determinant of selectivity of boldine and derivatives for the alpha 1A-adrenoceptor subtype.
1. The selectivity of action of boldine and the related aporphine alkaloids, predicentrine (9-O-methylboldine) and glaucine (2,9-O-dimethylboldine) and alpha 1-adrenoceptor subtypes was studied by examining [3H]-prazosin competition binding in rat cerebral cortex. WB 4101 and benoxathian were used as selective alpha 1A-adrenoceptor antagonists. 2. In the competition experiments [3H]-prazosin (0.2 nM) binding was inhibited by WB 4101 and benoxathian. The inhibition curves displayed shallow slopes which could be subdivided into high and low affinity components (pKi = 9.92 and 8.29 for WB 4101, 9.35 and 7.94 for benoxathian). The two antagonists recognized approximately 37% of the sites with h…