Modulation of postjunctional cholinergic sensitivity of rat diaphragm muscle by cyclic adenosine monophosphate

• Published in: The Journal of membrane biology Vol. 29; no. 1-2; pp. 67 - 79
• Main Author: Ewald, D A
• Format: Journal Article
• Language: English
• Published: United States 01-12-1976
• Subjects: Acetylcholine - pharmacology; Animals; Bucladesine - pharmacology; Cyclic AMP - analogs & derivatives; Cyclic AMP - pharmacology; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; Diaphragm; Membrane Potentials - drug effects; Muscle, Smooth - drug effects; Neuromuscular Junction - drug effects; Rats; Theophylline - pharmacology
• ISSN: 0022-2631; 1432-1424
• DOI: 10.1007/BF01868952

Addition of 2.5 mM cyclic adenosine monophosphate (cAMP) to the solution bathing a rat diaphragm muscle alters the magnitude of depolarization responses to iontophoretic pulses of acetylcholine (ACh) at neuromuscular endplates. Alterations are repeatable with small variability on a given preparation for initial and repeat experiments on both hemidiaphragms, but are different on each preparation. Five min after addition of the nucleotide solution, increases (potentiations) of up to 30% above control levels and decreases (attenuations) to 50% below control levels are observed. The effects on sensitivity to ACh of dibutyryl cAMP (1.25 mM), monobutyryl cAMP (0.25 mM), and cAMP (2.5 mM) in Ca++ -free solution are a function of whether the experiment is an initial one on that preparation or a repeat experiment after 10 or more minutes of perfusion flow. In all three cases, initial exposure attenuates sensitivity (means at 5 min: --30, --10, and --20%, respectively) and repeat exposure potentiates sensitivity (mean: 20% at 5 min, 15% at 5 min, and 10% at 2 min respectively). A concentration of dibutyryl cAMP (0.25 mM) which is without effect on sensitivity alone, produces a large, transient potentiation (mean: 45% at 1 min) in conjunction with 0.5 mM theophylline. A decrease in the rate of desensitization is observed during exposure to 0.25 mM cAMP. The results are interpreted in terms of a physiological mechanism whereby receptor activity at the postjunctional membrane is modulated by cAMP formed from prejunctionally released ATP.