H. Viko et al., ALPHA(1)-ADRENOCEPTOR SUBTYPES INVOLVED IN INCREASED RB-86-TRISPHOSPHATE MASS IN ADULT-RAT CARDIOMYOCYTES( INFLUX RATE AND INOSITOL 1,4,5), European journal of pharmacology, 323(2-3), 1997, pp. 269-275
The aim of the present study was to identify the receptor subtypes inv
olved in the alpha(1)-adrenoceptor-mediated increase in Rb-86(+) influ
x rate and in inositol 1,4,5-trisphosphate (IP3) accumulation in isola
ted ventricular cardiomyocytes from adult rat heart, in order to ident
ify a possible response pattern compatible with a causative relationsh
ip. Subtype-selective receptor antagonists used were: 5-methylurapidil
(alpha(1A)), WB 4101 ethoxyphenoxy-ethyl]aminomethyl)-1,4-benzodioxan
e} (alpha(1A)), chloroethylclonidine (alpha(1B)) and BMY 7378 iperazin
yl]ethyl]-8-azaspiro[4,5]decane-7,9-dione} (alpha(1D)). The basal Rb-8
6(+) influx rate was 0.22 +/- 0.01 ml/g protein x min. At 15 min, 5 x
10(-5) mol/l noradrenaline in the presence of 3 x 10(-5) mol/l timolol
increased the Rb-86(+) influx rate by 33 +/- 1%. This response was no
t affected by either chloroethylclonidine or BMY 7378 at concentration
s up to 10(-5) mol/L. 5-Methylurapidil dose dependently inhibited the
response to 5 x 10(-5) mol/l noradrenaline with a -logIC(50) value of
5.27 +/- 0.12 and 5.61 +/- 0.27 in the presence and absence of 10(-5)
mol/l chloroethylclonidine, respectively. WB 4101 in the presence of 1
0(-5) mol/l chloroethylclonidine dose dependently inhibited the respon
se to 5 x 10(-5) mol/l noradrenaline with a -logIC(50) value of 6.10 /- 0.14. Noradrenaline in the presence of 10(-5) mol/l chloroethylclon
idine dose dependently increased the Rb-86(+) uptake rate with a -logE
C(50) value of 6.19 +/- 0.35. The basal IP3 level was 2.15 +/- 0.19 pm
ol/mg protein. Incubation with 10(-5) mol/l noradrenaline for 2 min in
creased this by 65 +/- 7% of control levels. 10(-5) mol/l chloroethylc
lonidine and 10(-4) mol/15-methylurapidil reduced the response to 27 /- 6% and 18 +/- 9% of control level, respectively. BMY 7378 dose depe
ndently inhibited the IP3 response at relatively high concentrations,
and it was completely eliminated at 10(-5) mol/l BMY 7378. The combina
tion of chloroethylclonidine and 5-methylurapidil or 3 x 10(-6) mol/l
prazosin alone completely abolished the hormone-induced effect. We con
clude that whereas the alpha(1)-adrenoceptor-stimulated increase in Rb
-86(+) influx rate is mediated via the alpha(1A)-adrenoceptor subtype
only, both alpha(1A)- and alpha(1B)-adrenoceptor subtypes are involved
in the increase in IP3 mass. Furthermore, a contribution from the alp
ha(1D)-adrenoceptor in the IP3 response cannot be excluded. Thus there
does not appear to be a simple causative relationship between an incr
ease in Rb-86(+) influx rate and an increase in IP3. (C) 1997 Elsevier
Science B.V.