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Different bombesin receptor subtypes mediate contractile responses in the cat esophagus and fundus
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Abstracts from the 11 th hzternational Symposium on Regulatory Peptides
Increased NPYergie neurotransmission reduces hippocampal-induced s e i z u r e s : An autoregulatory mechanism Jens D. Mikkelsen*, David P.D. Woldbye#, Torsten M. Madsen#, Philip J. Larsen§, and Tom G. Bolwig# *Dept. Neurobiology, H. Lundbeck A/S, Valby-Copenhagen, #Laboratory for Experimental Nenropsychiatry, University Hospital, Rigshospitalet 6234, and §Dept Anatomy, University of Copenhagen, Copenhagen, Denmark Because the concentration of NPY in the cerebral cortex and hippocampus is increased in animals exposed to antidepressants or by repeated electrocouvulsive stimulations (ECS), NPY neurotransmission is proposed to be involved in the pathophysiology of endogenous depression. Further NPY (Yl) receptor blockade produce anxiolytic behavior in rats. Whether the increase of NPY neurotransmission by ECS is a beneficial component in antidepressive treatment is unknown. We first used quantitative in situ hybridisation histochemistry to compare the temporal relationship between the number of daily F_~S with the level of NPYmRNA in the hippocampus. A significant increase in NPY mRNA expression was achieved after the second stimulation in the hilar neurons of the dentate gyrus and in the piriform cortex, and the expression reached a maximal level (about 1000% over control) after 14 daily stimulations. Hence, a similar temporal correlation between the rise in NPY mRNA expression and the antidepressive effect of consecutive electroconvulsive treatments in depression was detected. Next, we tested whether seizures elicited by electrical stimulation of the dentate gyrus was affected by coadministration of NPY icv. Hippocampal EEG registration revealed that NPY reduced the primary afterdischarge duration and almost completely blocked the secondary after discharge. These observations imply that hippocampal NPY containing interneurons have an anticonvulsant effect in vivo. Whether the increased NPYergic neurotransmission and the resulting inhibition of the seizures are beneficial in the depressive state remains unresolved.
DIFFERENT BOMBES1N RECEPTOR SUBTYPES MEDIATE CONTRACTILE RESPONSES IN THE CAT ESOPHAGUS AND FUNDUS. E. Milusheva, Z. Mizhorkova, N. Kortezova, M. Papasova, *D.H. Coy, J~E.S. Vizi, JAG. Varga. Inst. Physiol., liulg. Acad. Sci., 1113 Sofia, Bulgaria; JDept. Med., Tulane Univ. Med. Center, New Orleans, LAT0112; JAlnst. Exp. Med., Hung. Acad. Sci., H-1450 Budapest, Hungary. The effects of C-terminal deeapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB) on the spontaneous contractions of musce strips isolated from cat esophagus and fundus were examined. Both GRP-10 and NMB evoked concentration-dependent contractions in the circular strips of esophagus and fundus which were TTX-resistant. The potency of NMB in esophageal strips was 33 times higher than that of GRP-10. The NMli-preffering receptor antagonists u-Nai-Cys-Tyr-D-TrpLys-VaI-Cys-NaI-NH 2 (SSocta) and D-Nal-cyclo[Cys-Tyr-D-Trp-Orn-VaI-Cys]-NaI-NH 2 (BIM-23127) shifted the dose-response curve for NMB to the right and decreased the maximal response to the agonist, while the GRP-preffering receptor antagonist [v-Phe6]Bombesin(6-13)-methyl-ester (liME) did not affect the response to NMli. Muscle strips from the cat fundus showed a higher sensitivity to GRP10 than to NMB. The respective ECs0 values were 3.7~-0.03 nM and 400A2.7 nM (nffi7). BME dose dependently shifted the GRP-10 concentration-response curve to the right, while SSocta had no effect. It is concluded that the direct myogenic action of GRP-10 and NMB in cat esophagus is mediated mainly via NMli-preffering receptors, while GRP-preffering receptors underlie the contractile responses in fundus. This work was partly supported by grant B-416 of the Bulgarian National Science Foundation.
Abstracts from the 11 th hzternational Symposium on Regulatory Peptides
Increased NPYergie neurotransmission reduces hippocampal-induced s e i z u r e s : An autoregulatory mechanism Jens D. Mikkelsen*, David P.D. Woldbye#, Torsten M. Madsen#, Philip J. Larsen§, and Tom G. Bolwig# *Dept. Neurobiology, H. Lundbeck A/S, Valby-Copenhagen, #Laboratory for Experimental Nenropsychiatry, University Hospital, Rigshospitalet 6234, and §Dept Anatomy, University of Copenhagen, Copenhagen, Denmark Because the concentration of NPY in the cerebral cortex and hippocampus is increased in animals exposed to antidepressants or by repeated electrocouvulsive stimulations (ECS), NPY neurotransmission is proposed to be involved in the pathophysiology of endogenous depression. Further NPY (Yl) receptor blockade produce anxiolytic behavior in rats. Whether the increase of NPY neurotransmission by ECS is a beneficial component in antidepressive treatment is unknown. We first used quantitative in situ hybridisation histochemistry to compare the temporal relationship between the number of daily F_~S with the level of NPYmRNA in the hippocampus. A significant increase in NPY mRNA expression was achieved after the second stimulation in the hilar neurons of the dentate gyrus and in the piriform cortex, and the expression reached a maximal level (about 1000% over control) after 14 daily stimulations. Hence, a similar temporal correlation between the rise in NPY mRNA expression and the antidepressive effect of consecutive electroconvulsive treatments in depression was detected. Next, we tested whether seizures elicited by electrical stimulation of the dentate gyrus was affected by coadministration of NPY icv. Hippocampal EEG registration revealed that NPY reduced the primary afterdischarge duration and almost completely blocked the secondary after discharge. These observations imply that hippocampal NPY containing interneurons have an anticonvulsant effect in vivo. Whether the increased NPYergic neurotransmission and the resulting inhibition of the seizures are beneficial in the depressive state remains unresolved.
DIFFERENT BOMBES1N RECEPTOR SUBTYPES MEDIATE CONTRACTILE RESPONSES IN THE CAT ESOPHAGUS AND FUNDUS. E. Milusheva, Z. Mizhorkova, N. Kortezova, M. Papasova, *D.H. Coy, J~E.S. Vizi, JAG. Varga. Inst. Physiol., liulg. Acad. Sci., 1113 Sofia, Bulgaria; JDept. Med., Tulane Univ. Med. Center, New Orleans, LAT0112; JAlnst. Exp. Med., Hung. Acad. Sci., H-1450 Budapest, Hungary. The effects of C-terminal deeapeptide of gastrin releasing peptide (GRP-10) and neuromedin B (NMB) on the spontaneous contractions of musce strips isolated from cat esophagus and fundus were examined. Both GRP-10 and NMB evoked concentration-dependent contractions in the circular strips of esophagus and fundus which were TTX-resistant. The potency of NMB in esophageal strips was 33 times higher than that of GRP-10. The NMli-preffering receptor antagonists u-Nai-Cys-Tyr-D-TrpLys-VaI-Cys-NaI-NH 2 (SSocta) and D-Nal-cyclo[Cys-Tyr-D-Trp-Orn-VaI-Cys]-NaI-NH 2 (BIM-23127) shifted the dose-response curve for NMB to the right and decreased the maximal response to the agonist, while the GRP-preffering receptor antagonist [v-Phe6]Bombesin(6-13)-methyl-ester (liME) did not affect the response to NMli. Muscle strips from the cat fundus showed a higher sensitivity to GRP10 than to NMB. The respective ECs0 values were 3.7~-0.03 nM and 400A2.7 nM (nffi7). BME dose dependently shifted the GRP-10 concentration-response curve to the right, while SSocta had no effect. It is concluded that the direct myogenic action of GRP-10 and NMB in cat esophagus is mediated mainly via NMli-preffering receptors, while GRP-preffering receptors underlie the contractile responses in fundus. This work was partly supported by grant B-416 of the Bulgarian National Science Foundation.