Volume 5(3): 136-141 (2013) - 136 J Bioequiv Availab ISSN:0975-0851 JBB, an open access journal Research Article Open Access Ayrapetyan et al., J Bioequiv Availab 2013, 5:3 DOI: 10.4172/jbb.1000148 Research Article Open Access *Corresponding author: Sinerik Ayrapetyan, UNESCO Chair-Life Sciences International Postgraduate Educational Center, 31 Acharyan St. 0040 Yerevan, Armenia, Tel: +374 10 624170; Fax: +374 10 624170; E-mail: info@biophys.am Received March 01, 2013; Accepted April 18, 2013; Published April 25, 2013 Citation: Ayrapetyan S, Heqimyan A, Deghoyan A (2013) Cell Dehydration as a Mechanism of Ketamine Analgesic and Anesthetic Effects. J Bioequiv Availab 5: 136-141. doi:10.4172/jbb.1000148 Copyright: © 2013 Ayrapetyan S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Effect of intraperitoneally (i.p.) injected sub-anesthetic (8×10 -5 -8×10 -2 mg/g) and anesthetic (0.1 mg/g) doses of ketamine on rats’ pain sensitivity and tissue hydration were studied. Determination of water content of tissue was performed by Adrian’s traditional “tissue drying” experimental procedure. The number of functionally active receptors were determined by counting the number of [ 3 H]-ouabain molecules in tissues. Latent period of pain sensitivity was defned by means of hot plate test. Ketamine in sub-anesthetic doses had depressing effect on rats’ latent period of pain sensitivity which was accompanied by tissues’ dehydration. [ 3 H]-ouabain infuence on brain tissues hydration was characterized by dose dependent three phases and this fact was accompanied by corresponding changes of ouabain receptors number in cell membrane. Ketamine in anesthetic dose had reversing effect on ouabain – induced cell hydration and it was different for each brain tissue. It was suggested that ketamine – induced cell dehydration leading to decrease of number of functional active proteins in membrane serves as a powerful mechanism through which an analgesic and anesthetic effects of ketamine on organisms were realized. Cell Dehydration as a Mechanism of Ketamine Analgesic and Anesthetic Effects Sinerik Ayrapetyan*, Armenuhi Heqimyan and Anush Deghoyan Life Sciences International Postgraduate Educational Center, 31 Acharyan St. 0040 Yerevan, Armenia Keywords: Rat; ketamine; [ 3 H]-ouabain receptor; Pain sensitivity; Cell hydration Introduction It is assumed that ketamine administration causes “dissociative anesthetic state” characterized by profound analgesic, moderate hypnotic properties and by marked sympathomimetic reactions. Its pharmacological profle cannot be explained by a single mechanism. Analgesic, anesthetic and sympathomimetic efects are mediated by diferent sides of action. It is suggested that N-methyl- D-aspartate (NMDA)-receptor antagonism accounts for most of the amnestic, analgesic, psychotomimetic and neuroprotective efects of ketamine [1,2]. Ketamine blocks an NMDA receptor-mediated component of synaptic transmission in a voltage-dependent manner [3-7]. Te ketamine depressing efect on variety of receptors is well established: nicotinic [8,9], muscarinic [10] and opioid ones [10-12], as well as on voltage sensitive Na + [9,13], K + [13-15] and Ca 2+ channels [16] of nerve cell membrane in peripheral and central nervous system. At present it is known that ketamine infuence is not limited only by nervous system but it has also relaxing efect on smooth and heart muscles [17-20] and other tissues [21]. However, the nature of cellular mechanism underlying in the ground of above mentioned multisided efects of ketamine on diferent tissues is not clear yet. Earlier on the basis of experimental data performed in vitro on snail single neurons the correlation between the number of functionally active membrane receptors having channel [22], receptor [23], enzyme functions [24] and active cell membrane surface was established. According to these data cell swelling leads to the activation, while shrinkage to the inhibition of neurons’ functional activity. Terefore, the metabolic control of cell volume-induced changes of membrane functional activity was suggested as an essential mechanism through which the regulation of neuronal ionic function is realized [25]. It is known that there are a number of non-conductive membrane mechanisms responsible for cell volume regulation such as Na + / K + pump, Na + /Ca ++ , Na + /H + exchangers, changes of cytoskeleton contractility and membrane fuidity and others [26]. Previously in vitro experiments (on snail neurons and women breast tissue) ketamine stimulating efect on Na + /K + pump and Na + /Ca ++ exchanger has been shown which brings to cell dehydration [27-29]. Terefore, the working hypothesis for present work was to clarify whether the ketamine- induced cell volume change has a crucial role in realization of analgesic and anesthetic efects as well as its multisided efect on diferent organs. For this purpose the dose-dependent efect of ketamine on rats’ pain sensitivity, hydration of diferent organs’ tissues and the number of [ 3 H]-ouabain receptors were studied. Materials and Methods All procedures performed on animals were carried out following the protocols approved by Animal Care and Use Committee of Life Sciences Postgraduate International Educational Center. Animals All experiments were performed on 180 adult male albino rats weighing from 100 g to 130 g. Animals were kept in a specifc pathogen- free animal room, under optimum conditions of 12 hours light/dark cycle and 22 ± 2°C temperature, received sterilized commercial diet and water ad libitum. Data were received from three independent experiments. For control group 5 animals were taken and injected intraperitoneally (i.p.) by 0.5 ml of physiological saline (PS). Five animal groups (5 rats in each) were used for each ketamine concentration injected by the same manner. Journal of Bioequivalence & Bioavailability J o u r n a l o f B i o e q u iv a l e n c e & B i o a v a i l a b i l i t y ISSN: 0975-0851