Functional GABAB receptors are present in guinea pig nodose ganglion cell bodies but not in peripheral mechanosensitive endings.
The effects of the GABAB-selective agonist baclofen were studied on guinea pig nodose ganglion neurones using grease gap and intracellular recording techniques, and on peripheral mechanosensitive endings in the guinea pig oesophagus and stomach with extracellular recordings. GABA dose-dependently reduced the amplitude of the compound action potential of C-type neurones (C spikes, EC50 = 30.9 microM), which was prevented by the GABAA antagonist bicuculline (10 microM). The GABAB agonist baclofen (1-300 microM) did not produce any significant effect on the amplitude of C spikes. In microelectrode studies, baclofen (100 microM) evoked hyperpolarisation (by 2.53 +/- 0.51 mV, n = 6, N = 5) in a subset of nodose neurones (6 out of 26, N = 18). In seven out of eight neurones (N = 8) with a slow after-hyperpolarisation following action potentials, baclofen significantly inhibited its amplitude by 19 +/- 4% (n = 7, p < 0.05). GABA (100 microM) evoked a depolarisation of 9.3 +/- 2.4 mV (10 nodose neurones, N = 9, p < 0.05) associated with a decrease in input impedance of 49 +/- 12% (N = 4, p < 0.05). Baclofen (100-200 microM) did not affect either spontaneous or stretch-evoked firing of distension-sensitive vagal mechanoreceptors of the guinea pig oesophagus and stomach but did inhibit mechanoreceptors in the ferret oesophagus. Antibodies to GABAB receptor 1a splice variants labelled most of the neurones and numerous fibres in the guinea pig nodose ganglion while antibodies to GABAB receptor 1b splice variants stained only nerve cell bodies. There were numerous nerve fibres showing GABAB receptor 1a- and 1b-like immunoreactivity in the myenteric plexus in the guinea pig oesophagus and stomach but not in anterogradely labelled extrinsic vagal nerve fibres. The result indicates that most guinea pig C-type nodose ganglion neurones have GABAB receptors on their cell bodies but their density on distension-sensitive peripheral endings is too low to allow modulation of mechanotransduction. There is a significant species-dependent difference in the expression of GABAB receptors on peripheral vagal mechanosensitive endings.
Zagorodnyuk
Vladimir P
VP
Department of Human Physiology, Centre for Neuroscience, Flinders University of South Australia, GPO Box 2100, Adelaide, South Australia, Australia. vladimir.zagorodnyuk@flinders.edu.au
D'Antona
Giuseppe
G
Brookes
Simon J H
SJ
Costa
Marcello
M
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D058786:GABA-B Receptor Agonists; D006168:Guinea Pigs; D008465:Mechanoreceptors / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D009411:Nerve Endings / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D036421:Nerve Fibers, Unmyelinated / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D009620:Nodose Ganglion / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D010525:Peripheral Nerves / Q000737:chemistry / Q000187:drug effects / Q000502:physiology; D018080:Receptors, GABA-B / Q000032:analysis / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D001418:Baclofen