Desensitization of the inhibition of the M-current in sympathetic neurons: effects of ATP analogs, polyanions, and multiple agonist applications.
Desensitization occurs when the response to a neurotransmitter receptor agonist wanes in the continued presence of agonist. In amphibian sympathetic neurons, both muscarinic and peptidergic receptor agonists inhibit a K+ current, the M-current (IM), and this inhibition desensitizes. We have studied the desensitization to substance P (SP) by whole-cell recordings from dissociated sympathetic neurons from bullfrogs. When ATP in the recording pipette was replaced with AMP-PNP, SP still inhibited IM, but no desensitization was observed, indicating that ATP hydrolysis is required for desensitization. Desensitization inhibitors of beta-adrenergic receptors did not block desensitization to SP. When a low dose of muscarine sufficient to inhibit IM, but not to elicit desensitization, was applied simultaneously with a desensitizing dose of SP, IM remained depressed and did not desensitize. Thus, there may be separate systems controlling desensitization for different agonists, or the enzyme(s) involved is "compartmentalized."
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
M A
MA
Simmons
J B
JB
Becker
R J
RJ
Mather
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases; D015536:Down-Regulation; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000502:physiology*; D009116:Muscarine / Q000494:pharmacology; D010766:Phosphorylation; D000071228:Polyelectrolytes; D011108:Polymers / Q000494:pharmacology; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D047428:Protein Kinase Inhibitors; D011892:Rana catesbeiana; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013373:Substance P / Q000494:pharmacology*; D051552:beta-Adrenergic Receptor Kinases
D000255:Adenosine Triphosphate; D017868:Cyclic AMP-Dependent Protein Kinases; D009116:Muscarine; D000071228:Polyelectrolytes; D011108:Polymers; D011188:Potassium; D015221:Potassium Channels; D047428:Protein Kinase Inhibitors; D011943:Receptors, Adrenergic, beta; D013373:Substance P; D051552:beta-Adrenergic Receptor Kinases