caa a22 4500 469078847 CHVBK 20180323132943.0 cr unu---uuuuu 170328e19920801xx s 000 0 eng 10.1007/BF00165303 doi (NATIONALLICENCE)springer-10.1007/BF00165303 Activation of histamine H3 receptors produces presynaptic inhibition of neurally evoked cat nictitating membrane responses in vivo [Elektronische Daten] [M. Koss, J. Hey] Summary: This study was undertaken in order to determine the potential role of prejunctional histamine H3 receptors in an in vivo adrenergic model system. Frequency-dependent nictitating membrane responses were elicited by sympathetic nerve stimulation in anesthetized cats. Systemic administration of the selective histamine H3 receptor agonist, (R)-α-methylhistamine (RαMeHA) produced a dose-related depression of amplitude of the evoked nictitating membrane responses with a threshold of about 10 μg/kg and maximal effect (50% depression at the lowest frequency; 0.5 Hz) seen at 100-300 gg/kg. Responses obtained with low frequency stimulation were more sensitive to depression by RaMeHA than were responses evoked with higher frequencies of stimulation. Larger doses of RaMeHA given to the same animals, failed to produce additional inhibition. RαMeHA depressed the amplitude of nictitating membrane responses evoked by either pre- or postganglionic nerve stimulation to an equivalent degree. This depressant action of RαMeHA was antagonized by pretreatment with the specific histamine H3 antagonist, thioperamide (3 mg/kg), but not by combined pretreatment with histamine H1 and H2 blockers chlorpheniramine (300 Ftg/kg) and cimetidine (5 mg/kg). Intravenous administration of adrenaline (1-30 wg/kg) also produced graded nictitating membrane responses that were not altered by subsequent administration of RαMeHA. These results suggest that histamine H3 receptors are involved in the modulation of neurally evoked noradrenaline release in the cat nictitating membrane by an inhibitory presynaptic action. The most likely site of drug action appears to be at the neuroeffector junction as no appreciable ganglionic effect of RαMeHA was observed in this in vivo model system. Springer-Verlag, 1992 Histamine H3 receptors nationallicence Cat nictitating membrane nationallicence (R)-α-Methylhistamine nationallicence Thioperamide nationallicence Presynaptic inhibition nationallicence Koss M. Department of Pharmacology, University of Oklahoma College of Medicine, 73190, Oklahoma City, OK aut Hey J. Department of Allergy, Schering-Plough Research, 07003, Bloomfield, NJ, USA aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/2(1992-08-01), 208-212 0028-1298 346:2<208 1992 346 210 https://doi.org/10.1007/BF00165303 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00165303 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Koss M. Department of Pharmacology, University of Oklahoma College of Medicine, 73190, Oklahoma City, OK aut NATIONALLICENCE 700 1- Hey J. Department of Allergy, Schering-Plough Research, 07003, Bloomfield, NJ, USA aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 346/2(1992-08-01), 208-212 0028-1298 346:2<208 1992 346 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer