Imidazoline I(2)-receptors and spinal reflexes in the decerebrated rabbit.
Idazoxan potentiates spinal reflexes in the decerebrated rabbit, an effect that has been attributed to antagonism of tonic noradrenergic inhibition. It is now known that this drug has a higher affinity for I(2)-imidazoline receptors than alpha(2)-receptors. The roles of I(2)-receptors in modulating transmission in spinal reflex pathways have been investigated using the selective ligands RX 821029 and RS-45041-190, and, as I(2)-receptors are closely associated with monoamine oxidase (MAO), the MAO inhibitors pargyline and clorgyline. In decerebrated rabbits with an intact spinal cord, intrathecal doses of 5-365 microg (cumulative) of the I(2)-ligands augmented, to 150-180% of pre-drug levels, the reflex responses of medial gastrocnemius motoneurones to electrical stimulation of the sural nerve, and significantly increased mean arterial blood pressure by approximately 10 mmHg over pre-drug values. Neither MAO inhibitor had significant effects on reflexes, but the highest dose of the MAO-A selective agent clorgyline (365 microg cumulative) caused a significant rise in blood pressure of 6 mmHg. Neither the I(2)-ligands nor the MAO inhibitors prevented the further enhancement of reflexes or blood pressure by subsequent administration of the selective alpha(2)-adrenoceptor antagonist RX 821002. In decerebrated, spinalized rabbits, intrathecal RS-45041-190 (60 microg, single dose) increased spinal reflex responses to 109% of pre-drug values, a significantly smaller effect than that seen in non-spinal preparations, and had no effect on blood pressure. These data show that imidazoline I(2)-receptors can influence somatic and autonomic motor outflows. These effects should be taken into account when interpreting the spinal effects of imidazoline-based adrenoceptor-active drugs.
Clarke
R W
RW
Division of Animal Physiology, School of Biological Sciences, University of Nottingham, Sutton Bonington Campus, Leics, LE12 5RD, Loughborough, UK. robert.clarke@nottingham.ac.uk
Harris
J
J
Ogilvie
J
J
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003010:Clorgyline / Q000494:pharmacology; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D019329:Idazoxan / Q000031:analogs & derivatives / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D007211:Indoles / Q000494:pharmacology; D007278:Injections, Spinal; D054833:Isoindoles; D008024:Ligands; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D010293:Pargyline / Q000494:pharmacology; D011817:Rabbits; D011955:Receptors, Drug / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D054755:Imidazoline Receptors; D007211:Indoles; D054833:Isoindoles; D008024:Ligands; D008996:Monoamine Oxidase Inhibitors; D011955:Receptors, Drug; C097364:4-chloro-2-(imidazolin-2-yl)isoindoline; D010293:Pargyline; C058525:2-methoxyidazoxan; D003010:Clorgyline; D019329:Idazoxan