Premium
Effects of a new α‐adrenoceptor blocking agent, ethyl‐7‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]heptanoate dihydrochloride (SGB‐483), on smooth muscle and neuromuscular transmission in guinea‐pig mesenteric artery
Author(s) -
Fujisawa K.
Publication year - 1983
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.1476-5381.1983.tb11049.x
Subject(s) - prazosin , depolarization , yohimbine , neuromuscular transmission , membrane potential , phenylephrine , chemistry , stimulation , guinea pig , medicine , endocrinology , biophysics , antagonist , biology , biochemistry , receptor , blood pressure
1 The effects of ethyl‐7‐[4‐(2‐methoxyphenyl)‐l‐piperazinyl] heptanoate dihydrochloride (SGB‐483) on the smooth muscle of the guinea‐pig mesenteric artery were investigated using microelectrodes. 2 The resting membrane potential was — 70.3 ± 2.1 mV. SGB‐483 (10 −8 M ‐ 10 −4 M ) did not modify the membrane potential or membrane resistance, as estimated from measurement of current‐voltage relationships. 3 Noradrenaline (NA; above 10 −5 M ) depolarized the membrane. After pretreatment with SBG‐483 10 −5 M or prazosin 10 −6 M , the NA‐induced depolarization of the membrane was inhibited; yohimbine (10 −5 M ) was ineffective. Phenylephrine and NA (> 3 × 10 −7 M ) but not clonidine (10 −6 M ) contracted the artery. These contractions were inhibited by SGB‐483. 4 Following repetitive perivascular nerve stimulation, the amplitude of excitatory junction potentials (e.j.ps) increased to a certain steady state value (e.j.p.(s)). The amplitude of e.j.p.(s) was frequency‐dependent. Application of SGB‐483 (over 10 −8 M ) enhanced the amplitude of e.j.p.(s), dose‐dependently with no change in the amplitude of the first e.j.p. (e.j.p.(f)) evoked by the first stimulus. 5 After pretreatment with NA, the amplitudes of both e.j.p.(f) and e.j.p.(s) were inhibited, dose‐dependently. Following pretreatment with SGB‐483 (10 −6 ‐10 −5 M ), the NA‐induced reduction in the amplitude of both e.j.p.(f) and e.j.p.(s) were reversed and the control values restored. 6 Clonidine (10 −7 M ) inhibited the amplitude of e.j.p.(f) and e.j.p.(s), and SGB‐483 (10 −7 M ) partially restored the amplitude of both. 7 Yohimbine (10 −7 M ) and phentolamine (10 −7 M ) enlarged the amplitude of e.j.p.(s); the amplitude of e.j.p.(f) was inhibited by yohimbine and enlarged by phentolamine. Prazosin (10 −6 M ) had no effect on the amplitude of either e.j.p.(f) or e.j.p.(s), at any given stimulus frequency. SBG‐483 (10 −7 M ) did not enhance the amplitudes of either e.j.p.(f) or e.j.p.(s) following pretreatment with phentolamine (10 −7 M ) or yohimbine (10 −7 M ) but did enhance the amplitude following pretreatment with prazosin (10 −7 M ). 8 SGB‐483 possesses the property of an α 1 ‐ and α 2 ‐adrenoceptor antagonist. The α‐antagonistic action was apparent on post‐junctional smooth muscle cells. The α 2 ‐antagonistic action on neuromuscular transmission was mediated at pre‐junctional nerve terminals to enhance the release of NA. The prejunctional actions of SGB‐483 were more selective than those of yohimbine or phentolamine.