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."
Simmons
M A
MA
Department of Pharmacology, Marshall University School of Medicine, Huntington, West Virginia 25755-9310.
Becker
J B
JB
Mather
R J
RJ
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