The Journal of Neurophysiology Vol. 85 No. 5 May 2001, pp. 1888-1898
Copyright ©2001 by the American Physiological Society

Differential Expression of Functionally Identified and Immunohistochemically Identified NK₁ Receptors on Sympathetic Neurons

Department of Anatomy and Histology and Centre for Neuroscience, Flinders University of South Australia, Adelaide, SA 5001, Australia

Jobling, Phillip, Jennifer P. Messenger, and Ian L. Gibbins. Differential Expression of Functionally Identified and Immunohistochemically Identified NK₁ Receptors on Sympathetic Neurons. J. Neurophysiol. 85: 1888-1898, 2001. 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.