title: Functional and morphological characteristics of neuronal substance P in the canine gastroesophageal junction.
abstract: The specific functions of the numerous substance P (SP) nerve fibers present within the gastrointestinal tract are not clearly defined. This study examines both functional aspects and distribution of immunoreactive SP (IR-SP) in the canine gastroesophageal junctional (GEJ) region. Lower esophageal sphincter pressure (LESP), mean arterial pressure (MAP), pulse rate (PR), and respiratory rate (RR) were monitored before and after topical application of 2 ml capsaicin (8-methyl-N-vanillyl-6-nonenamide) to the distal esophageal mucosa of anesthetized dogs. Animals then underwent a capsaicin desensitization protocol over a 12-day period. The responses of monitored variables were compared on Day 1 and Day 12 of repetitive capsaicin application. Immunohistochemistry and radioimmunoassay (RIA) were performed on GEJ segments to study the distribution and content of IR-SP in both control (untreated) and capsaicin-treated dogs. The IR-SP was extracted from tissue for RIA and analysis by reverse-phase high-performance liquid chromatography (HPLC). On Day 1, a 2-ml capsaicin application stimulated increases in LESP (44.3 +/- 7.8 cm H2O; P < 0.05), MAP (48 +/- 8.7 mm Hg; P < 0.05), PR (52.6 +/- 20.5 beats/min; P < 0.05), and RR (26.3 +/- 15.6 breaths/min; P > 0.2). No response was observed on Day 12 of treatment. This was accompanied by a 43.3% decrease of IR-SP content in the mucosa of the distal esophagus of desensitized animals. Capsaicin applied at greater concentrations on Day 12 stimulated a return of responses (P < 0.05). Ganglia, cell bodies, nerve fascicles, and neurites stained positively for IR-SP. IR-SP content was markedly higher in esophageal mucosa than in gastric mucosa (P < 0.05). The authenticity of the IR-SP molecule was confirmed by elution time on HPLC. In conclusion, repetitive capsaicin application induced a state of homologous desensitization which was accompanied by a partial depletion of mucosal SP. The GEJ region contains a high SP content with a broad neural distribution. These findings are consistent with the hypothesis that SP may act as a neurotransmitter for chemonociceptive stimuli in the canine distal esophagus.
authors.affiliation: Department of Surgery, University of Iowa College of Medicine, Iowa City 52242.
authors.forename: A D
authors.initials: AD
authors.lastname: Sandler
authors.forename: J W
authors.initials: JW
authors.lastname: Maher
authors.forename: J V
authors.initials: JV
authors.lastname: Weinstock
authors.forename: C D
authors.initials: CD
authors.lastname: Schmidt
authors.forename: J F
authors.initials: JF
authors.lastname: Schlegel
authors.forename: J Y
authors.initials: JY
authors.lastname: Jew
authors.forename: T H
authors.initials: TH
authors.lastname: Williams
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004947:Esophagus / Q000737:chemistry / Q000294:innervation / Q000502:physiology*; D007150:Immunohistochemistry; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000737:chemistry; D011312:Pressure; D011674:Pulse / Q000187:drug effects; D011863:Radioimmunoassay; D012119:Respiration / Q000187:drug effects; D013270:Stomach / Q000737:chemistry / Q000294:innervation / Q000502:physiology*; D013373:Substance P / Q000032:analysis / Q000502:physiology*
chemical_list: D013373:Substance P; D002211:Capsaicin