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Smooth muscle and parasympathetic nerve terminals in the rat urinary bladder have different subtypes of α 1 adrenoceptors
Author(s) -
Széll E A,
Yamamoto T,
De Groat W C,
Somogyi G T
Publication year - 2000
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 - 10.1038/sj.bjp.0703475
Subject(s) - endocrinology , medicine , stimulation , atropine , acetylcholine , phenylephrine , chemistry , cholinergic , agonist , muscle contraction , urinary bladder , receptor , blood pressure
Neurally evoked contractions and release of 3 H‐ acetylcholine (ACh) during electrical field stimulation were measured in rat urinary bladder strips. The α 1 agonist phenylephrine (PE, 2–8 μ M ) increased the amplitude of neurally evoked contractions, facilitated the release of ACh and increased the baseline tone of the bladder strips. The PE‐induced facilitation of the contractions did not significantly change during a prolonged exposure to PE (120 min), whereas the PE‐induced rise in baseline tone gradually decreased to 65% of the initial value. Low concentrations of specific α 1A antagonists, 5‐methyl urapidil (5‐MU), REC15/2739 and WB‐4101 competitively inhibited the facilitation of the neurally‐evoked contractions (pA 2: 8.77; 9.59 and 9.62, respectively), whereas higher concentrations of 5‐MU (IC 50 : 48 n M ) were required to suppress the PE‐rise in baseline. WB‐4101 (100 μ M ) inhibited the PE‐induced facilitation of ACh release. The irreversible α 1B antagonist chloroethyl‐clonidine (CEC, 10–50 μ M ) inhibited the PE‐evoked rise in base line tone, but did not affect the PE‐induced facilitation of the neurally evoked contractions nor the facilitation of ACh release. However, CEC increased the area and amplitude of the neurally‐evoked contractions by 261±33 and 47.2±8.4%, respectively. Atropine significantly inhibited the CEC evoked increase in area and amplitude of the electrically evoked contractions (76.5±4.8 and 40.8±3%, respectively) indicating that CEC facilitated the cholinergic responses of the electrically stimulated bladder strips. It is concluded that α 1A and CEC sensitive α 1B and/or α 1D adrenoceptors are expressed in the rat bladder in different locations. On the cholinergic nerve terminals α 1A adrenoceptors mediate prejunctional facilitation, whereas postjunctional α 1B /α 1D adrenoceptors mediate smooth muscle contraction.British Journal of Pharmacology (2000) 130 , 1685–1691; doi: 10.1038/sj.bjp.0703475