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Photodynamic action of aluminium phthalocyanine tetrasulphonate (A1PcS 4 ) on smooth muscle: effects of thiols and a cyclic GMP analogue
Author(s) -
Matthews E.K.,
Flaherty C.,
Smith W.H.T.
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.tb13949.x
Subject(s) - contraction (grammar) , carbachol , chemistry , muscle contraction , glutathione , cysteamine , dithiothreitol , calcium , muscle relaxation , biophysics , endocrinology , medicine , biochemistry , biology , receptor , organic chemistry , enzyme
1 The smooth muscle system of the guinea‐pig taenia caeci has been used in vitro to characterize the photodynamic action of aluminium phthalocyanine tetrasulphonate (AlPcS 4 ) in the presence or absence of the thiol reductants l ‐cysteine (Cys), N‐acetyl‐ l ‐cysteine (NAC), dl ‐dithiothreitol (DTT) or reduced glutathione (GSH). 2 In all photodynamic experiments the muscle was exposed to AlPcS 4 (10 −5 m ) for 30 min, followed by a 30 min washout period before photon irradiation at 32,000 lux (Λ > 570 nm) for 30 min. Photodynamic contractions were measured relative to the contractile response to carbachol (5 × 10 −5 m ) and relaxation responses were determined in muscle precontracted with either carbachol 5 × 10 −5 m or KCl 23.5 m m . 3 Photon‐activation of AlPcS 4 ‐sensitized smooth muscle evoked a triphasic response: an initial transient contraction and subsequent relaxation followed by a secondary sustained contraction. Cys 10 m m , NAC 10 m m and DTT 5 m m had no effect on the initial photodynamic contraction but significantly decreased the magnitude of the sustained contraction from mean values of 98% to 18%, 95% to 72% and 93% to 6% of the standard carbachol contraction (5 × 10 −5 m ), respectively; GSH 10 m m was without significant effect on either the initial or sustained contraction. 4 In the absence of extracellular calcium the AlPcS 4 ‐sensitized smooth muscle did not respond to photon activation but re‐introduction of calcium after cessation of illumination produced a sustained contraction which was markedly inhibited by Cys 10 m m . 5 In precontracted AlPcS 4 ‐treated muscle preparations photon activation produced a triphasic relaxation response, i.e. a rapid relaxation followed by a transient contraction and a secondary more sustained relaxation. The sustained phase of photodynamic relaxation was potentiated significantly by Cys 10 m m , NAC 10 m m , DTT 5 m m and GSH 10 m m , the relaxation being approximately doubled in magnitude from mean values of 34% to 68%, 30% to 73%, 34% to 68%, and 48% to 77%, respectively, relative to the standard carbachol (5 × 10 −5 m ) response. 6 The cyclic GMP analogue, 8‐(4‐chlorophenylthio)‐guanosine‐3′: 5′‐cyclic monophosphate (8‐PCPT‐cGMP) (2 × 10 −4 m ) alone caused a triphasic relaxation response similar to that produced by photon activation of an AlPcS 4 ‐sensitized precontracted preparation in the presence of thiol reductants. The pattern of 8‐PCPT‐cGMP‐induced relaxation was similar in muscle precontracted with carbachol 5 × 10 −5 m or KCl 23.5 m m . 7 It is concluded that the rapid generation of reactive intermediates by photon‐activation of bound AlPcS 4 leads to membrane permeabilization, calcium entry and muscle contraction. These effects may be opposed by a direct stimulatory action of singlet oxygen on guanylate cyclase which is enhanced by the action of thiol reagents and mimicked by the cyclic GMP analogue, 8‐PCPT‐cGMP.