title: Blockade of neurokinin-1 receptors in the ventral respiratory column does not affect breathing but alters neurochemical release.
abstract: Substance P (SP) and its receptor, neurokinin-1 (NK1R), have been shown to be excitatory modulators of respiratory frequency and to stabilize breathing regularity. Studies in anesthetized mice suggest that tonic activation of NK1Rs is particularly important when other excitatory inputs to the pre-Bötzinger complex in the ventral respiratory column (VRC) are attenuated. Consistent with these findings, muscarinic receptor blockade in the VRC of intact goats elicits an increase in breathing frequency associated with increases in SP and serotonin concentrations, suggesting an involvement of these substances in neuromodulator compensation. To gain insight on the contribution to breathing of endogenous SP and NK1R activation, and how NK1R modulates the release of other neurochemicals, we individually dialyzed antagonists to NK1R (133, 267, 500 μM Spantide; 3 mM RP67580) throughout the VRC of awake and sleeping goats. We found that NK1R blockade with either Spantide at any dose or RP67580 had no effect on breathing or regularity. Both antagonists significantly (P < 0.001) increased SP, while RP67580 also increased serotonin and glycine and decreased thyrotropin-releasing hormone concentrations in the dialysate. Taken together, these data support the concept of neuromodulator interdependence, and we believe that the loss of excitatory input from NK1Rs was locally compensated by changes in other neurochemicals.
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors: Clarissa
authors: C
authors: Muere
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors: Suzanne
authors: S
authors: Neumueller
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors: Samantha
authors: S
authors: Olesiak
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin.
authors: Justin
authors: J
authors: Miller
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin;
authors: Matthew R
authors: MR
authors: Hodges
authors: Department of Physical Therapy, Marquette University, Milwaukee, Wisconsin; and.
authors: Lawrence
authors: L
authors: Pan
authors: Department of Physiology, Medical College of Wisconsin, Milwaukee, Wisconsin; Zablocki Veterans Affairs Medical Center, Milwaukee, Wisconsin bforster@mcw.edu.
authors: Hubert V
authors: HV
authors: Forster
mesh_terms: D000818:Animals; D005260:Female; D005998:Glycine / Q000378:metabolism; D006041:Goats; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012119:Respiration / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D012890:Sleep / Q000187:drug effects; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D011976:Receptors, Muscarinic; D018040:Receptors, Neurokinin-1; D012701:Serotonin; D013373:Substance P; C042867:spantide; D005998:Glycine
keywords: control of breathing; neurokinin-1 receptor; neuromodulator interdependence; substance P
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