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Contractions mediated by α 1 ‐adrenoceptors and P 2 ‐purinoceptors in a cat colon circular muscle
Author(s) -
Venkova Kalina,
Milne Andrew,
Krier Jacob
Publication year - 1994
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.1476-5381.1994.tb13216.x
Subject(s) - prazosin , medicine , endocrinology , phenylephrine , adenosine , propranolol , agonist , muscle contraction , purinergic receptor , chemistry , antagonist , biology , receptor , blood pressure
1 The postjunctional excitatory and inhibitory effects of adrenoceptor and purinoceptor agonists and antagonists were studied in circular smooth muscle strips of cat colon. 2 In the presence of tetrodotoxin (0.5 μ m ), noradrenaline caused contraction or relaxation of circular smooth muscle at resting tension or with raised tone, respectively. The noradrenaline‐evoked contractions were potentiated and the noradrenaline‐evoked relaxations were antagonized by propranolol (1 μ m ), suggesting β‐adrenoceptor involvement. 3 At resting tension, noradrenaline, adrenaline and the selective α 1 ‐adrenoceptor agonist, phenylephrine, caused concentration‐dependent contractile responses, with EC 50 values of 1.8 ± 0.2 μ m , 1.9 ± 0.4 μ m and 4.3 ± 1.7 μ m , respectively. The EC 50 values and the amplitude of maximal responses were not significantly different from one another. Clonidine (0.1–500 μ m ), a selective α 2 ‐adrenoceptor agonist, was not effective. 4 Prazosin (0.1–9 μ m ), competitively antagonized the contractile effects of noradrenaline with an estimated pA 2 value of 6.93 and a slope of 1.07 ± 0.03. The K b values, estimated from a single shift (0.1 μ m prazosin) of the concentration‐response curves to noradrenaline, adrenaline and phenylephrine were 92.8 ± 9.3 nM, 108.7 ± 6.4 nM and 18.4 ± 3.1 nM, respectively. 5 At resting tension, adenosine 5′ triphosphate (ATP, 5–1000 μ m ), α,β‐methylene adenosine 5′‐triphosphate (α,β‐MeATP, 0.05–50 μ m ), β,γ‐methylene adenosine 5′‐triphosphate (β,γ‐MeATP, 0.5–100 μ m ), and 2‐methylthioadenosine 5′‐triphosphate (2‐MeSATP, 1–500 μ m ) caused concentration‐dependent contractions with EC 50 values of 60.5 ± 15.9 μ m , 0.7 ± 0.1 μ m , 7.6 ± 0.1 μ m and 25.3 ± 12.8 μ m , respectively. The maximal responses to α,β‐MeATP and β,γ‐MeATP were greater than maximal responses to 2‐MeSATP and ATP. 6 Suramin (50–500 μ m ), competitively antagonized the contractile responses of α,β‐MeATP with an estimated pA 2 value of 4.92 and a slope of 1.08 ± 0.04. The K b values, estimated from a single shift (100 μ m suramin) of the concentration‐response curves to ATP, α,β‐MeATP, β,γ‐MeATP and 2MeSATP were 52.3 ± 20.2 μ m , 25.2 ± 4.5 μ m , 21.7 ± 11.0 μ m and 11.6 ± 2.7 μ m , respectively. 7 At resting tension, reactive blue 2 (100 μ m ), a selective antagonist of the P 2Y ‐purinoceptor, and 8‐( p ‐sulphophenyl)‐theophylline (8‐SPT) (1 μ m ), a selective antagonist of the P 1 ‐purinoceptor, did not antagonize the contractile responses to α,β‐MeATP (0.5–5 μ m ). Contractile responses to ATP (50–500 μ m ) were not altered by 8‐SPT (1 μ m ) but were potentiated by reactive blue 2 (100 μ m ). 8 With raised tone, ATP and 2‐MeSATP caused a relaxant effect. This effect of ATP was not altered by either tetrodotoxin (TTX) (0.5 μ m ) or suramin (100 μ m ), but was antagonized by reactive blue 2 (100 μ m ) and 8‐SPT (1 μ m ), suggesting that inhibitory P 2Y ‐ and P 1 ‐purinoceptors are involved. In contrast, α,β‐MeATP and β,γ‐MeATP caused only contractions. This contractile effect of α,β‐MeATP was resistant to TTX (0.5 μ m ) and antagonized by suramin (100 μ m ). 9 In summary, cat colon circular muscle contains postjunctional α 1 ‐adrenoceptors and P 2X ‐purinoceptors which mediate contractions and P 2Y ‐ and P 1 ‐purinoceptors which mediate relaxation. Postjunctional α 2 ‐adrenoceptors appear not to be present.