Sensitivity changes in guinea-pig atria and ileum following subacute administration of dyflos

1. Subacute administration of dyflos to guinea-pigs (1.2 mg/kg, s.c., daily for 10 days) led to the development of subsensitivity to carbachol in the ileum but not in the electrically stimulated left atrium. 2. Atria from dyflos-pretreated animals became supersensitive to acetylcholine but the ileum became subsensitive to this agonist despite marked inhibition of cholinesterases. The degree of subsensitivity was less than that for carbachol. 3. Subsensitivity also developed to histamine and was of a similar order to that observed for carbachol supporting the suggestion that subsensitivity is a nonspecific post-receptor mechanism. 4. Other changes which occurred in the ileum, together with the increase in the EC50 value to agonists were an increase in tissue mass, an increase in the slope of the concentration-response curve to agonists and an increase in the maximal response to agonists.