ALPHA(1)-ADRENOCEPTOR SUBTYPES INVOLVED IN INCREASED RB-86-TRISPHOSPHATE MASS IN ADULT-RAT CARDIOMYOCYTES( INFLUX RATE AND INOSITOL 1,4,5)

Citation
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
Citations number
27
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
323
Issue
2-3
Year of publication
1997
Pages
269 - 275
Database
ISI
SICI code
0014-2999(1997)323:2-3<269:ASIIIR>2.0.ZU;2-B
Abstract
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.