We have used multiple-labeling immunohistochemistry, intracellular dye-filling, and intracellular microelectrode recordings to characterize the distribution of tachykinin receptors and substance P boutons on subpopulations of neurons within the guinea pig celiac ganglion. Superfusion of substance P (SP, 1 μM for 1 min) depolarized 42% of tonic neurons and inhibited afterhyperpolarizations in 66% of long afterhyperpolarizing (LAH) neurons without significant desensitization. Twenty-one percent of tonic neurons and 24% of LAH neurons responded to the NK3 agonist senktide but did not respond to SP, indicating SP did not activate NK3 receptors at this concentration. All effects of SP were abolished by the selective NK1 receptor antagonist, SR140333, but not by the selective NK3 receptor antagonist, SR142801, suggesting that exogenous SP activated a receptor with NK1 pharmacology. No dye-filled LAH neuron and only 50% of tonic neurons responding to SP expressed NK1 receptor immunoreactivity (NK1-IR). All neurons responding to SP had SP immunoreactive fibers within one cell diameter, indicating good spatial matching between SP release sites and target neurons. These results indicate that SP may act via a receptor with NK1-like pharmacology that has a C terminus not recognized by antibodies to the intracellular domain of the conventional NK1 receptor. Inward currents evoked by SP acting on this NK1-like receptor or senktide acting through NK3 receptors had identical current-voltage relationships. In LAH neurons, both agonists suppressed I sAHP without reducing I AHP. Responses evoked by SP and senktide were resistant to PKC inhibitors, suggesting that the transduction mechanisms for the NK1-like receptor and the NK3 receptor may be similar.
Solubilization of a membrane factor that stimulates levels of substance P and choline acetyltransferase in sympathetic neurons.