Loss of [125I]-pindolol binding to beta-adrenoceptors on rat nodose ganglion after chronic isoprenaline treatment.
The nodose ganglion contains the cell bodies of afferent nerves which convey predominantly sensory information from the viscera to the central nervous system (CNS). Autoradiographic studies show binding sites for beta-adrenoceptor ligands are present on sections of the rat nodose ganglion and also on the corresponding inferior vagal ganglion in humans, indicating the presence of beta-adrenoceptors in these ganglia. Since prolonged stimulation of beta-adrenoceptors in rats with the nonselective beta-adrenoceptor agonist isoprenaline (400 micrograms kg-1 day-1 s.c.) for 14 days results in desensitisation and/or down-regulation of receptors in peripheral tissues, such as heart, kidney and blood vessels, the effects of this treatment on the beta-adrenoceptor population on the nodose ganglion have been examined. Using [125I]-pindolol as a radioligand, autoradiographic studies revealed that specific binding was reduced by 74% in ganglia from isoprenaline-pretreated rats compared to that in ganglia from vehicle-pretreated rats, demonstrating down-regulation of receptors by isoprenaline. [125I]-Pindolol binding was sensitive to inhibition by ICI 118.551 (selective beta 2-adrenoceptor antagonist) but not to atenolol (selective beta 1-adrenoceptor antagonist), indicating receptors are predominantly of the beta 2-adrenoceptor subtype. No change in binding was apparent over the vagus nerve. The nodose ganglion appears to be an additional site at which beta 2-adrenoceptors may be down-regulated in vivo, possibly interfering with normal baro-, chemo- and sensory reflexes.
Watkins
D J
DJ
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Lawrence
A J
AJ
Lewis
S J
SJ
Jarrott
B
B
D000818:Animals; D001667:Binding, Competitive; D015536:Down-Regulation / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009620:Nodose Ganglion / Q000187:drug effects*; D010869:Pindolol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D010869:Pindolol; D007545:Isoproterenol