title: Serotonin 5-HT7 receptor agonist, LP-211, exacerbates Na(+), K(+)-ATPase/Mg(2+)-ATPase imbalances in spinal cord-injured male rats.
abstract: BACKGROUND
  The observed controversy that N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211), a selective serotonin (5-HT7) receptor agonist, may either modify or exacerbate imbalances in serum electrolyte concentrations and renal tissue of spinal cord trauma cases has not been reported yet. The aim of this study was to better understand the effects of a new 5-HT7 receptor agonist, LP-211, on serum electrolyte changes in spinal cord injured- (SCI) rats.
  
  
  METHODS
  Sixty male rats were assigned to the following groups: A) Intact (saline as vehicle, 1 ml/kg, i.p.), B) Intact [LP-211, (0.003-0.3 mg/kg, i.p.)], C) Sham-operated [laminectomy + vehicle (1 ml/kg, i.p.)], D) Sham-operated [laminectomy + LP-211 (0.003-0.3 mg/kg, i.p.)], E) Treatment [laminectomy + spinal trauma (SCI) + vehicle (1 ml/kg, i.p.)], F) Treatment [laminectomy + spinal trauma + LP-211 (0.003-0.3 mg/kg, i.p.)]. SCI was performed by placing an aneurysm clip, extradurally at the level of T10. After two weeks, LP-211 was administered cumulatively and each dose was injected (i.p.) with 20 min interval. At the end of the experiment, blood samples were collected for biochemical evaluations of the electrolytes employing standard commercial kits.
  
  
  RESULTS
  The present results indicate elevated serum levels of Na(+), K(+), and Mg(2+) in SCI rats and significant differences demonstrated between the groups [P < 0.001, F(5, 35) = 23.92], [P < 0.001, F(5, 35) = 67.63], [P < 0.001, F(5, 35) = 71.144], respectively. So that, in groups B, D and F, there was a significant increase in K(+) and Mg(2+) serum levels compared to the groups A, C, and E (P < 0.001). Furthermore, Na(+) serum levels in SCI (LP-211), laminectomy (LP-211), and intact (LP-211) groups tended to be statistically lower than SCI (saline), laminectomy (saline) and intact (saline) groups. Infact, hyponatremia, hyperkalemia and hypermagnesemia was obtained in group F. Nevertheless, in the remaining measured serum electrolytes such as calcium (Ca(2+)), iron (Fe(2+)) and phosphorus (P(3-)), chlorine (Cl(-)), copper (Cu(+)), and zinc (Zu(+)), no significant changes were observed.
  
  
  CONCLUSIONS
  It was shown that acute additive LP-211 treatments in the SCI group led to hyponatremia, hyperkalemia and hypermagnesemia, it may be stated that LP-211 treatment as a promising candidate for treating SCI complications in some systems especially urinary tract might take into consideration and further studies would be needed to clarify its benefits or drawbacks. The observed discrepancies, nevertheless; will also pose new questions. Altogether, this will ultimately contribute to further understanding the pathophysiological role regarding 5-HT7 receptor activation.
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Norouzi-Javidan
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Javanbakht
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fardin
authors.initials: F
authors.lastname: Barati
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Fakhraei
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Mohammadi
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.|Experimental Medicine Research Center, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. dehpour@yahoo.com.|Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran. dehpour@yahoo.com.
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004573:Electrolytes / Q000097:blood; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D027682:Cation Transport Proteins; D004573:Electrolytes; C573815:N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide; D018696:Neuroprotective Agents; D010879:Piperazines; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D000251:Adenosine Triphosphatases; C035214:potassium magnesium ATPase; C021838:sodium-translocating ATPase