Beta3 adrenoceptors substitute the role of M 2 muscarinic receptor in coping with cold stress in the heart: Evidence from M 2KO mice

We investigated the role of beta3-adrenoceptors (AR) in cold stress (1 or 7 days in cold) in animals lacking main cardioinhibitive receptors - M2 muscarinic receptors (M 2KO). There was no change in receptor number in the right ventricles. In the left ventricles, there was decrease in binding to all cardiostimulative receptors (beta1-, and beta2-AR) and increase in cardiodepressive receptors (beta3-AR) in unstressed KO in comparison to WT. The cold stress in WT animals resulted in decrease in binding to beta1- and beta2-AR (to 37%/35% after 1 day in cold and to 27%/28% after 7 days in cold) while beta3-AR were increased (to 216% of control) when 7 days cold was applied. MR were reduced to 46% and 58%, respectively. Gene expression of M2 MR in WT was not changed due to stress, while M3 was changed. The reaction of beta1- and beta2-AR (binding) to cold was similar in KO and WT animals, and beta3-AR in stressed KO animals did not change. Adenylyl cyclase activity was affected by beta3-agonist CL316243 in cold stressed WT animals but CL316243 had almost no effects on adenylyl cyclase activity in stressed KO. Nitric oxide activity (NOS) was not affected by BRL37344 (beta3-agonist) both in WT and KO animals. Similarly, the stress had no effects on NOS activity in WT animals and in KO animals. We conclude that the function of M2 MR is substituted by beta3-AR and that these effects are mediated via adenylyl cyclase rather than NOS. © Springer Science+Business Media, LLC 2011

Kainic Acid and Nitrergic Neurons Kainic Acid and Nitrergic Neurons in Immature Hippocampus

Jandová K.; Riljak V.; Pokorný J.; Langmeier M. Abstract: Using histochemical analysis the effect of intraperitoneal administration of kainic acid on hippocampal neurons was studied. 18-day-old male rats of the Wistar strain received kainic acid (10mg/kg) in one dose. Two days later, the 20-day-old animals were transcardially perfused with 4% paraformaldehyde under deep thiopental anaesthesia. Cryostat sections were stained to identify NADPH-diaphorase positive neurons that were then quantified in the CA1 and CA3 areas of the hippocampus, in the dorsal and ventral blades of the dentate gyrus and in the hilus of the dentate gyrus. Combination of the Fluoro-Jade B and bis-benzimide (Hoechst 33342) was used in the same areas, to identify possible neurodegeneration. After the kainic acid administration the number of NADPH-d positive neurons was lower in CA1 and CA3 areas of the hippocampus and in the hilus of the dentate gyrus, compared to the control group which we consider as baseline. Fluoro-Jade B staining detected a moderate density of neurodegeneration after KA administration in CA3 and CA1 areas of the hippocampus and the hilus of the dentate gyrus