Ketamine inhibits contractile responses of intestinal smooth muscle by decreasing the influx of calcium through the L-type calcium channel.
During the inflammatory response, tissues release histamine (H), substance P, serotonin (5-HT), prostaglandins and kinins, agents that mediate manifestations of inflammation such as pain, vasodilation, increased capillary permeability and smooth muscle contraction. In this study we investigated whether racemic (R[+]) ketamine (K) and its isomers are spasmolytic on intestinal smooth muscle contracted by inflammatory mediators, and whether the spasmolytic effect of K is related to changes in calcium influx through the L-type calcium channel or to an interaction of K with opioid receptors. We measured the contractions of guinea-pig ileum mounted in an organ bath containing Tyrode's solution gassed with 95% O2/5% CO2 at 37 degrees C. In the first protocol we determined the effect of K and its isomers on contractions induced by five mediators: 10(-7) M H, 10(-8) M substance P, 10(-8) M neurokinin A, 5 x 10(-9) M bradykinin and 5 x 10(-7) M 5-HT. For each of these mediators, we plotted concentration-response curves for the inhibitory effect of K, and from regression fitting of these curves, we calculated the IC50 concentration of K that inhibited the contraction by 50%). In the second protocol we measured the contraction induced by the calcium ionophore A23187 (5.0 x 10(-6) M), both alone and after 1.8-7.2 x 10(-4) M R(+/-)K. Then we examined how the inhibition caused by R(+/-)K was affected by increases in the concentration of extracellular calcium by adding calcium (1.8-7.2 x 10(-3) M).(ABSTRACT TRUNCATED AT 250 WORDS)
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007649:Ketamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009270:Naloxone / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology
D015220:Calcium Channels; D018836:Inflammation Mediators; D007476:Ionophores; D010276:Parasympatholytics; D009270:Naloxone; D000001:Calcimycin; D007649:Ketamine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D002118:Calcium