UTP‐ and ATP‐triggered transmitter release from rat sympathetic neurones via separate receptors

Abstract

In rat cultured sympathetic neurones, UDP, UTP and ATP at micromolar concentrations triggered Ca2"-dependent and tetrodotoxin-sensitive [3H]-noradrenaline release. The overflow evoked by UTP or ATP was similar at 100 ,umol I', the concentration used in all subsequent experiments. Pre-exposure of the neurones to 100 pumol I' UTP significantly reduced ensuing secretory effects of UTP but not of ATP. Conversely, pre-exposure to ATP diminished the overflow due to ATP but not that due to UTP. In the presence of 10 pmol I`pyridoxal-5'-phosphate or 30 pmol 1' suramin, the secretory response to ATP was reduced, but the effect of UTP was unaltered. Zn2+ (10 imol I-') reduced the overflow triggered by UTP, but increased the overflow due to ATP. These results indicate the presence of separate receptors for pyrimidine nucleotides and for purine nucleotides which both trigger transmitter release.

Modulation of Spontaneous and Stimulation‐Evoked Transmitter Release from Rat Sympathetic Neurons by the Cognition Enhancer Linopirdine: Insights into Its Mechanisms of Action

“…ATP, nicotine, or 25 mM K' triggered transmitter release in a partially TTX-resistant manner, and the release remaining in the presence of TTX was not enhanced by linopirdine. These TTX-resistant components of stimulation-evoked release involve direct stimulatory actions at presynaptic sites (Boehm and Huck, 1995;Boehm, 1999). Hence, linopirdine appears unable to enhance noradrenaline release via a presynaptic site of action, which supports the idea that K, channels are located at the somatodendritic region rather than at presynaptic axon terminals of SCG neurons.…”

“…Previously, activation of either nicotinic acetylcholine receptors (Boehm and Huck, 1995) or ATP P2X receptors (Boehm, 1999) has been found to trigger noradrenaline release from SCG neurons in a partially TTXsensitive manner. Therefore, the above experiments were repeated with nicotine (100 p M ) or ATP (300 pM) as secretory stimuli.…”

Dual coupling of heterologously‐expressed rat P2Y6 nucleotide receptors to N‐type Ca2+ and M‐type K+ currents in rat sympathetic neurones

“…Thus, UTP inhibits the M-current and excites some sympathetic neurones (e.g., Siggins et al, 1977;Adams et al, 1982;Cuevas et al, 1997); while Von Kugelgen et al (1994) have described inhibitory eects of UTP on evoked transmitter release from brain tissue (though the receptors responsible for these eects have not been fully characterized). On the other hand, UTP and UDP (but not ATP) have been reported to trigger transmitter release from sympathetic terminals through a P2Y receptor (Boehm et al, 1995;Von Kugelgen et al, 1997): this could be related to the increase in intracellular Ca 2+ following phospholipase C stimulation. The balance between inhibitory and facilitatory eects on transmitter release might then be dierent in peripheral and central nerve terminals because of the complement of receptors/eectors involved.…”

Molecular Physiology of P2X Receptors

“…The calcium flux through the P2X receptors is sufficient to evoke the release of norepinephrine. Boehm et al (30,31) showed that norepinephrine was released by ATP from cultures for rat superior cervical ganglion cells, even when voltage-gated calcium channels were blocked by cadmium (see also Ref. 487).…”