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) ar e distributed in interneurons throughout the central nervous system of the locust Locusta migratoria and may have important roles as neurotr ansmitters or neuromodulators. In search of the central actions of Lom TKs, 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 filli ng of efferent DUM neurons with Lucifer yellow, revealed that LomTK-im munoreactive 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 ma de from somata of DUM neurons, and LomTKs were either bath-applied to an isolated metathoracic ganglion or pressure-ejected onto the DUM neu ron soma. LomTK I at concentrations of 0.1 mM-0.1 mu M caused a relati vely slow, reversible depolarization with a subsequent increase in the frequency of action potential firing. Amino-terminally truncated form s of LomTK 1 were applied to DUM neurons. The heptapeptide [3-9]-LomTK 1 had a substantially reduced activity, and bioactivity was lost afte r further truncation. Spantide 1, an antagonist of mammalian tachykini n receptors, reversibly blocked the effect of LomTK 1. The effect of L omTK 1 was clearly reduced in the presence of GDP-beta-S, a stable ana log of GDP that inactivates G-proteins. The action of LomTK 1 was pote ntiated by both IBMX and theophylline, two cyclic AMP (cAMP) phosphodi esterase inhibitors. The action of LomTK 1 was mimicked by pressure-ej ecting 8-bromo-cAMP, a membrane permeable analog of cAMP, and by forsk olin, an adenylate cyclase activator. Furthermore, cAMPS, a blocker of protein kinase A activity, reduced the effect of LomTK 1. These findi ngs indicate that cAMP is involved in mediating DUM neuron depolarizti on. (C) 1997 John Wiley & Sons, Inc. J Neurobiol.