Peptidergic activation of locust dorsal unpaired median neurons: depolarization induced by locustatachykinins may be mediated by cyclic AMP.
Four tachykinin-related peptides, locustatachykinin 1-4 (LomTK 1-4) are distributed in interneurons throughout the central nervous system of the locust Locusta migratoria and may have important roles as neurotransmitters or neuromodulators. In search of the central actions of LomTKs, we analyzed the response of the efferent dorsal unpaired median (DUM) neurons in the locust metathoracic ganglion. Immunocytochemistry, using an antiserum against LomTK 1, combined with intracellular filling of efferent DUM neurons with Lucifer yellow, revealed that LomTK-immunoreactive fibers are in close proximity to dendritic arborizations of the DUM neurons. Hence, LomTKs may act on DUM neurons by releasing locally in the metathoracic ganglion. Intracellular recordings were made from somata of DUM neurons, and LomTKs were either bath-applied to an isolated metathoracic ganglion or pressure-ejected onto the DUM neuron soma. LomTK 1 at concentrations of 0.1 mM-0.1 microM caused a relatively slow, reversible depolarization with a subsequent increase in the frequency of action potential firing. Amino-terminally truncated forms of LomTK 1 were applied to DUM neurons. The heptapeptide [3-9]-LomTK 1 had a substantially reduced activity, and bioactivity was lost after further truncation. Spantide 1, an antagonist of mammalian tachykinin receptors, reversibly blocked the effect of LomTK 1. The effect of LomTK 1 was clearly reduced in the presence of GDP-beta-S, a stable analog of GDP that inactivates G-proteins. The action of LomTK 1 was potentiated by both IBMX and theophylline, two cyclic AMP (cAMP) phosphodiesterase inhibitors. The action of LomTK 1 was mimicked by pressure-ejecting 8-bromo-cAMP, a membrane permeable analog of cAMP, and by forskolin, an adenylate cyclase activator. Furthermore, cAMPS, a blocker of protein kinase A activity, reduced the effect of LomTK 1. These findings indicate that cAMP is involved in mediating DUM neuron depolarization.
Lundquist
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Department of Zoology, Stockholm University, Sweden.
Nässel
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D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000918:Antibody Specificity; D000242:Cyclic AMP / Q000378:metabolism*; D003712:Dendrites / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology; D019204:GTP-Binding Proteins / Q000378:metabolism; D017952:Ganglia, Invertebrate / Q000166:cytology; D006110:Grasshoppers / Q000502:physiology*; D019476:Insect Proteins / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D008274:Magnesium / Q000494:pharmacology; D009474:Neurons / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D009479:Neuropeptides / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000032:analysis / Q000276:immunology / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000700:Analgesics; D019476:Insect Proteins; D009479:Neuropeptides; D015320:Tachykinins; C063413:locustatachykinin I protein, Locusta migratoria; C063414:locustatachykinin II protein, Locusta migratoria; C068632:locustatachykinin III protein, insect; C068633:locustatachykinin IV protein, insect; D013373:Substance P; D013779:Tetrodotoxin; C042867:spantide; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D008274:Magnesium