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EFFECTS OF CATECHOLAMINES, CYCLIC NUCLEOTIDES AND PHOSPHODI‐ESTERASE INHIBITORS ON CONTRACTIONS OF SKELETAL MUSCLES IN ANAESTHETIZED CATS
Author(s) -
Bowman W. C.,
Nott M. W.
Publication year - 1974
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1974.tb00553.x
Subject(s) - cats , nucleotide , chemistry , medicine , endocrinology , biochemistry , gene
SUMMARY 1. The actions and interactions of compounds with phosphodiesterase‐in‐hibiting activity and of sympathomimetic amines have been studied on contractions of skeletal muscles in chloralose‐anaesthetized cats treated with bethanidine and in which the adrenals were excluded from the circulation. 2. Compounds with phosphodiesterase‐inhibiting activity, ICI 63,197, ICI 58,301, papaverine, theophylline, and dipyridamole, potentiated isoprenaline in its depressant effect on tension and fusion of incomplete tetanic contractions of the slow‐contracting soleus muscle, the order of potency being as listed. ICI 63,197 and theophylline also potentiated adrenaline and salbutamol in depressing contractions. 3. ICI 63,197 potentiated isoprenaline in its enhancing effect on tension and degree of fusion of incomplete tetanic contractions of the fast‐contracting tibialis anterior and flexor digitorum longus muscles. 4. The results are compatible with the hypothesis that the effects of sympathomimetic amines on muscle contractility are mediated by cyclic adenosine‐3',5'‐monophosphate, although this nucleotide and its dibutyryl analogue, injected intra‐arterially, were themselves without any consistent effect. 5. High doses of ICI 63,197, ICI 58,301, papaverine and dipyridamole, themselves produced isoprenaline‐like effects on the soleus muscle. These effects were partially antagonized by (±)‐propranolol, (+)‐propranolol, or sotalol. The (+)‐isomer of propranolol was only about ten times less potent than racemic propranolol in this respect. This antagonistic action of propranolol and sotalol appeared to be independent of β‐adrenoceptor blockade.