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Relation between α 1 ‐adrenoceptor subtypes and noradrenaline‐induced contraction in rat portal vein smooth muscle
Author(s) -
Sayet Irène,
Neuilly Ghislaine,
Rakotoarisoa Lala,
Mironneau Chantal,
Mironneau Jean
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13793.x
Subject(s) - prazosin , contraction (grammar) , chemistry , yohimbine , vascular smooth muscle , endocrinology , medicine , muscle contraction , phentolamine , sarcolemma , biophysics , antagonist , receptor , biochemistry , biology , smooth muscle , membrane
1 In vascular smooth muscle, α 1 ‐adrenoceptors have been classified recently into two or three subtypes. We examined which α 1 ‐adrenoceptor subtypes are involved in the noradrenaline‐induced contraction of rat portal vein smooth muscle. 2 Binding studies with [ 3 H]‐prazosin in membranes from equine portal vein smooth muscle revealed the presence of two distinct affinity binding sites. The high‐affinity site for [ 3 H]‐prazosin was also identified in intact strips of rat portal vein. Prazosin, HV723 (α‐ethyl‐3,4,5‐trimethoxy‐α‐(3‐((2‐(2‐methoxyphenoxy)ethyl)‐amino)‐propyl) benzene‐acetonitrile fumarate), WB4101 (2‐(2,6‐dimethoxyphenoxyethyl)aminomethyl‐1,4‐benzodioxane), 5‐methylurapidil, phentolamine and yohimbine antagonized [ 3 H]‐prazosin binding at both types of sites. Pretreatment with 50 μ m chloroethylclonidine (CEC) eliminated the high‐affinity sites for prazosin but had no effect on the low‐affinity sites. 3 Noradrenaline produced a concentration‐dependent contraction in the rat portal vein. Pretreatment with 50 μ m CEC induced a slight rightward displacement of the concentration‐response curve but the maximal contraction was not significantly affected suggesting that the CEC‐sensitive α 1 ‐adrenoceptors played a minor role in the noradrenaline‐induced contraction. Prazosin, WB4101 and HV723 produced a concentration‐dependent inhibition of noradrenaline‐induced contractions. The inhibition curves were little affected by CEC‐pretreatment and yielded a relative order of potency of WB4101 > prazosin > HV723. 4 In the presence of 0.1 μ m isradipine to block voltage‐dependent Ca 2+ channels, the noradrenaline‐induced contraction is due to release of Ca 2+ ions from agonist‐sensitive intracellular Ca 2+ stores. Under these conditions, the noradrenaline‐induced contraction was not significantly affected by pretreatment with 50 μ m CEC but was inhibited by the antagonists mentioned above with affinities different from those in the absence of isradipine. The rank order of potency became HV723 ≥ WB4101 > prazosin. 5 The present results indicate the existence of two distinct α 1 ‐adrenoceptor subtypes in rat portal vein smooth muscle, which show high‐ and low‐affinities respectively for each of prazosin, WB4101 and HV723 and correspond to α 1H ‐ and α 1L ‐adrenoceptor subtypes. According to recent α 1 ‐adrenoceptor subclassifications, the α 1H ‐adrenoceptor subtype which is sensitive to inactivation by CEC may correspond to the α 1B ‐adrenoceptor subtype. The contraction induced by noradrenaline seems to be predominantly mediated through the α 1L ‐adrenoceptor subtypes which may include the α 1N ‐adrenoceptor subtype, as recently proposed.