ISSN:
1432-1912
Keywords:
Dopamine DA1 receptors
;
Dopamine
;
cAMP
;
Rabbit splenic artery
;
IBMX
;
Forskolin
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary Dopamine relaxes precontracted rabbit isolated splenic arteries via stimulation of dopamine DA1 receptors on the smooth muscle. However, in many preparations, the effect of dopamine is small. In an attempt to increase the effectiveness of dopamine and thus increase the proportion of usable preparations, we have examined the effects, on the sensitivity of dopamine, of the phosphodiesterase inhibitor 3-isobutyl-l-methylxanthine (IBMX) and the adenylate cyclase stimulant forskolin. In tissues pretreated with phenoxybenzamine, and in the presence of propranolol, IBMX (1 µmol/1) or forskolin (0.01 µmol/1) produced a small increase in the sensitivity to dopamine in otherwise insensitive preparations. The maximum relaxation of U-46619-induced tone produced by dopamine was increased to around 50%. However, after treatment with higher concentrations of IBMX (10 µmol/1) or forskolin (0.1 µmol/1), previously insensitive preparations relaxed readily to dopamine with EC50 values in the range 1–3 µmol/1. Similarly, in spontaneously dopamine-sensitive preparations IBMX (1 µmol/1) or forskolin (0.01 µmol/1) produced only a 2–3-fold parallel shift to the left in the dopamine concentration-effect curves. However, higher concentrations of IBMX (10 µmol/1) or forskolin (0.1 µmol/1) produced 10–20-fold parallel shifts to the left in dopamine concentration-effect curves. Higher concentrations of IBMX (100 µmol/1) or forskolin (1 µmol/1) abolished the ability of the spasmogen to contract the preparations. The potency of the dopamine receptor antagonists SCH 23390 and sulpiride, and the potency, relative to dopamine, of the agonists epinine, 6,7-ADTN, N,N-di-n-propyldopamine, and SK&F 38393 were similar in ring preparations treated with IBMX (10 µmol/1) to those experienced previously using untreated strip preparations. This suggests that dopamine-induced relaxation is mediated by the same type of vascular dopamine DA1 receptors whether in the presence or absence of IBMX. SK&F 82526 appeared to act as a partial agonist. In both dopamine-sensitive and dopamine-insensitive splenic artery strip preparations, from which the endothelium had been removed, IBMX (10 µmo1/1) produced a marked increase in the sensitivity to dopamine, which was comparable with that observed in splenic artery ring preparations. This suggests that the increase in sensitivity produced by IBMX in ring preparations is not dependent upon the presence of the vascular endothelium. This study shows that the sensitivity of the rabbit isolated splenic artery to dopamine can be increased by treatment with IBMX or forskolin which supports the view that the relaxant effect of dopamine in this preparation is mediated via activation of adenylate cyclase.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00260608
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