Modulatory effects of alpha1-,alpha2-, and beta -receptor agonists on feline spinal interneurons with monosynaptic input from group I muscle afferents.
Previous studies have shown that monoamines may modulate operation of spinal neuronal networks by depressing or facilitating responses of the involved neurons. Recently, activation of interneurons mediating reciprocal inhibition from muscle spindle (Ia) afferents and nonreciprocal inhibition from muscle spindle and tendon organ (Ia/Ib) afferents in the cat was found to be facilitated by noradrenaline (NA). However, which subclass membrane receptors are involved in mediating this facilitation was not established; the aim of the present experiments was to investigate this. Individual Ia- and Ia/Ib-inhibitory interneurons were identified in the cat lumbar spinal cord, and NA agonists were applied close to these neurons by ionophoresis. The agonists included the alpha1-receptor agonist phenylephrine, the alpha2-receptor agonists clonidine and tizanidine, and the beta-receptor agonist isoproterenol. Effects were measured by comparing changes in the number of extracellularly recorded spike potentials evoked by electrical stimulation of muscle nerves and changes in the latency of these potentials before, during, and after application of the tested compounds. Results show that the facilitatory effect of phenylephrine is as strong as that of NA, whereas the facilitatory effect of isoproterenol is weaker. Clonidine depressed activity of both Ia- and Ia/Ib-inhibitory interneurons, whereas tizanidine had no effect. These findings lead to the conclusion that beneficial antispastic effects of clonidine and tizanidine in humans are unlikely to be associated with an enhancement of the actions of Ia- and Ia/Ib-inhibitory interneurons, and the findings also support previous proposals that these compounds exert their antispastic actions via effects on other neuronal populations.
Hammar
Ingela
I
Department of Physiology, Göteborg University, 405 30 Göteborg, Sweden. Ingela.Hammar@physiol.gu.se
Jankowska
Elzbieta
E
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000344:Afferent Pathways; D000818:Animals; D002415:Cats; D003000:Clonidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019054:Evoked Potentials, Motor; D005260:Female; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D009470:Muscle Spindles / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation*; D009433:Neural Inhibition; D010656:Phenylephrine / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology*; D009435:Synaptic Transmission
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010656:Phenylephrine; C023754:tizanidine; D007545:Isoproterenol; D003000:Clonidine