The oxytocin-induced inward current in vagal neurons of the rat is mediated by G protein activation but not by an increase in the intracellular calcium concentration

Autor: Jean Jacques Dreifuss, Mario Raggenbass, Stefano Alberi
Jazyk: angličtina
Rok vydání: 1997
Předmět:
Calcium/ metabolism
Male
Patch-Clamp Techniques
8-Bromo Cyclic Adenosine Monophosphate
Oxytocin
Hippocampus
Calcium in biology
Adenylyl cyclase
Rats
Sprague-Dawley
chemistry.chemical_compound
Forskolin/pharmacology
Guanosine 5'-O-(3-Thiotriphosphate)/pharmacology
Hippocampus/cytology/metabolism
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
Cyclic AMP
Excitatory Amino Acid Agonists
Cyclic AMP/analogs & derivatives/metabolism/pharmacology
N-Methylaspartate/pharmacology
Enzyme Inhibitors
Neurons
Enzyme Inhibitors/pharmacology
Forskolin
General Neuroscience
Oxytocin/ pharmacology
Vagus Nerve
Excitatory Amino Acid Agonists/pharmacology
Thionucleotides/pharmacology
GTP-Binding Proteins/ metabolism
medicine.medical_specialty
N-Methylaspartate
Oxytocin receptor binding
Neuropeptide
Biology
Buffers
BAPTA
GTP-Binding Proteins
Internal medicine
medicine
Animals
Protein kinase A
Vagus Nerve/cytology/drug effects/ physiology
Colforsin
Thionucleotides
ddc:616.8
Rats
Neurons/drug effects/metabolism/physiology
Endocrinology
Dorsal motor nucleus
chemistry
Guanosine 5'-O-(3-Thiotriphosphate)
Calcium
Brain Stem/cytology
Brain Stem
Zdroj: European Journal of Neuroscience, Vol. 9, No 12 (1997) pp. 2605-2612
ISSN: 0953-816X
Popis: The neuropeptide oxytocin can depolarize parasympathetic preganglionic neurons in the dorsal motor nucleus of the vagus nerve of the rat by generating a sustained inward current, which is sodium-dependent and tetrodotoxin-insensitive. The second messenger activated by oxytocin receptor binding is, however, not yet known. In the present study, we attempted to characterize it by using the whole-cell recording technique and brainstem slices. When loaded with GTP-gamma-S, a non-hydrolysable analogue of GTP, vagal neurons generated a persistent inward current in the absence of agonist and the oxytocin effect was suppressed, suggesting that the peptide-evoked current was mediated by G-protein activation. Loading vagal neurons with the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N',-tetraacetic acid (BAPTA) suppressed a calcium-dependent, slowly decaying potassium aftercurrent but did not affect the oxytocin response, suggesting that the latter was not mediated by an agonist-induced increase in the intracellular calcium concentration. Protein kinase C (PKC) activation was probably not involved, since the peptide-evoked current was not modified by loading neurons with the PKC inhibitor H7. Thus, the oxytocin-evoked current in vagal neurons was probably not mediated by phospholipase C-beta (PLC-beta) activation. Loading neurons with 8-Br-cAMP or with an adenylyl cyclase activator (forskolin) reduced the oxytocin-evoked current by about half. SQ 22536, an adenylyl cyclase inhibitor, reduced this current by a similar amount. However, the peptide-evoked current was unaffected by Rp-cAMPS and Sp-cAMPS, an inhibitor and an activator, respectively, of cAMP-dependent protein kinase (PKA). We suggest that oxytocin activates two distinct signalling pathways in vagal neurons: one which is cAMP-dependent, but PKA-independent, and one, unidentified, which is PLC-beta-and cAMP-independent. Each pathway accounts for about half of the peptide effect and both appear to involve G-protein activation.
Databáze: OpenAIRE
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