title: Substance P-saporin lesion of neurons with NK1 receptors in one chemoreceptor site in rats decreases ventilation and chemosensitivity.
abstract: All medullary central chemoreceptor sites contain neurokinin-1 receptor immunoreactivity (NK1R-ir). We ask if NK1R-ir neurons and processes are involved in chemoreception. At one site, the retrotrapezoid nucleus/parapyramidal region (RTN/Ppy), we injected a substance P-saporin conjugate (SP-SAP; 0.1 pmol in 100 nl) to kill NK1R-ir neurons specifically, or SAP alone as a control. We made measurements for 15 days after the injections in two groups of rats. In group 1, with unilateral injections made in the awake state via a pre-implanted guide cannula, we compared responses within rats using initial baseline data. In group 2, with bilateral injections made under anaesthesia at surgery, we compared responses between SP-SAP- and SAP-treated rats. SP-SAP treatment reduced the volume of the RTN/Ppy region that contained NK1R-ir neuronal somata and processes by 44 % (group 1) and by 47 and 40 % on each side, respectively (group 2). Ventilation (.V(E)) and tidal volume (V(T)) were decreased during air breathing in sleep and wakefulness (group 2; P < 0.001; two-way ANOVA) and P(a,CO2) was increased (group 2; P < 0.05; Student's t test). When rats breathed an air mixture containing 7 % CO(2) during sleep and wakefulness, .V(E) and V(T) were lower (groups 1 and 2; P < 0.001; ANOVA) and the Delta.V(E) in air containing 7 % CO(2) compared to air was decreased by 28-30 % (group 1) and 17-22 % (group 2). SP-SAP-treated rats also slept less during air breathing. We conclude that neurons with NK1R-ir somata or processes in the RTN/Ppy region are either chemosensitive or they modulate chemosensitivity. They also provide a tonic drive to breathe and may affect arousal.
authors.affiliation: Department of Physiology, Dartmouth Medical School, Borwell Building, Lebanon, NH 03756-0001, USA. Eugene.Nattie@Dartmouth.edu
authors.forename: Eugene E
authors.initials: EE
authors.lastname: Nattie
authors.forename: Aihua
authors.initials: A
authors.lastname: Li
mesh_terms: D000818:Animals; D002628:Chemoreceptor Cells / Q000502:physiology*; D004338:Drug Combinations; D000922:Immunotoxins / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism*; D009699:N-Glycosyl Hydrolases / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010940:Plant Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D012119:Respiration; D054789:Ribosome Inactivating Proteins, Type 1; D000076985:Saporins; D012890:Sleep / Q000187:drug effects; D013373:Substance P / Q000494:pharmacology*
chemical_list: D004338:Drug Combinations; D000922:Immunotoxins; D010940:Plant Proteins; D018040:Receptors, Neurokinin-1; D054789:Ribosome Inactivating Proteins, Type 1; D013373:Substance P; D009699:N-Glycosyl Hydrolases; D000076985:Saporins