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Are acetylcholine‐induced increases in 42K efflux mediated by intracellular cyclic GMP in turtle cardiac pace‐maker tissue?
Author(s) -
Fleming B P,
Giles W,
Lederer J
Publication year - 1981
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1981.sp013689
Subject(s) - acetylcholine , intracellular , efflux , cyclic gmp , chemistry , microbiology and biotechnology , turtle (robot) , biophysics , medicine , endocrinology , biology , biochemistry , fishery , enzyme
1. 42K efflux has been measured from small strips of turtle sinus venosus tissue in order: (a) to characterize further the pharmacology of the acetylcholine response and (b) to test whether cyclic guanosine 3':5'‐monophosphoric acid (cyclic GMP) is the intracellular mediator of this response. 2. The 42K wash‐out curves show that the fractional escape rate (FER) of 42K efflux is nearly constant after 60‐80 min, indicating that after this time period 42K FER is controlled by barrier‐limited diffusion from a single intracellular compartment. 3. The threshold of the dose‐response relationship for the acetylcholine‐induced increase in 42K FER is about 10(‐8) M and the Km is 2.75 x 10(‐7) in non‐eserinized preparations. 4. This acetylcholine response is completely blocked by atropine; but nicotinic blockers produce no detectable reduction of it. 5. Exogenous application of lipid‐soluble analogues of cyclic GMP (dibutyryl or 8‐bromo‐cyclic GMP applied at 2‐3 mM for 30 min) failed to mimic the acetylcholine‐induced augmentation of 42K FER. 6. Experiments in which sodium nitroprusside (5 x 10(‐4) M for 30 min) was applied in order to stimulate the guanylate cyclase and hence produce a large, maintained increase in intracellular cyclic GMP failed to show a significant increase in 42K FER. 7. When acetylcholine (10(‐6)M) was applied in the presence of O[Ca2+]0 (in an attempt to inhibit the guanylate cyclase) there was no significant reduction in the acetylcholine‐induced increases in 42K FER. 8. Hence, these three indirect tests indicate that the muscarinic acetylcholine‐induced increase in 42K FER in cardiac pace‐maker tissue is unlikely to be mediated entirely by changes in the levels of intracellular cyclic GMP.