title: Cardiovascular and respiratory activity of PK20, opioid and neurotensin hybrid peptide in anesthetized and awake rats.
abstract: OBJECTIVE
  Chimeric compound - PK20 despite its therapeutic activity on nociceptive and inflammatory processes may affect respiration and blood pressure. Our objective was to evaluate influence of the hybrid composed of endomorphin-2 and neurotensin fragments on ventilation, heart rate and blood pressure in anesthetized and awake rats.
  
  
  METHODS
  The effects of PK20 (1mg/kg) were studied either after its intravenous administration in anesthetized rats or intraperitoneal injection in awake state. Tidal volume and the timing components of the breathing pattern, arterial blood pressure, and heart rate were recorded.
  
  
  RESULTS
  Intravenous administration of PK20 in the neurally intact rats evoked a dose-dependent apnoea followed by a transient insignificant increase in tidal volume and breathing rate. The blood pressure changes were biphasic: transient increase was replaced by prolonged hypotension. Midcervical vagotomy abrogated all post-PK20 respiratory effects. Hypotension was eliminated after blockade of neurotensin NTS1receptor, while respiratory changes were reduced by blockade of both: NTS1and μ opioid receptors. After PK20 intraperitoneal injection awake rats did not show any significant changes in ventilation and blood pressure.
  
  
  CONCLUSIONS
  This chimeric peptide should be used with care via intravenous administration in anesthetized animals since PK20 may evoke respiratory apnoea and hypotension. Nevertheless, applied intraperitoneally in the same dose in conscious rats induced no adverse effects.
authors.affiliation: Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland. Electronic address: kkaczynska@imdik.pan.pl.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kaczyńska
authors.affiliation: Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wojciechowski
authors.affiliation: Laboratory of Respiration Physiology, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Jampolska
authors.affiliation: Department of Neuropeptides, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland.
authors.forename: Andrzej W
authors.initials: AW
authors.lastname: Lipkowski
authors.affiliation: Department of Neuropeptides, Mossakowski Medical Research Centre Polish Academy of Sciences, Warsaw, Poland; Department of Pharmacodynamics, Centre for Preclinical Research and Technology, Medical University of Warsaw, Poland.
authors.forename: Patrycja
authors.initials: P
authors.lastname: Kleczkowska
mesh_terms: D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*
chemical_list: D009842:Oligopeptides; C000616899:PK20 peptide
keywords: Analgesic chimera; Cardiorespiratory effects; Endomorphin-2; Hybrid peptide; Neurotensin