Extracellular ATP-induced calcium channel inhibition mediated by P1/P2Y purinoceptors in hamster submandibular ganglion neurons.

Abstract

1. The presence and profile of purinoceptors in neurons of the hamster submandibular ganglion (SMG) have been studied using the whole-cell configuration of the patch-clamp technique. 2. Extracellular application of adenosine 5'-triphosphate (ATP) reversibly inhibited voltage-dependent Ca(2+) channel (VDCC) currents (I(Ca)) via G(i/o)-protein in a voltage-dependent manner. 3. Extracellular application of uridine 5'-triphosphate (UTP), 2-methylthioATP (2-MeSATP), alpha,beta-methylene ATP (alpha,beta-MeATP) and adenosine 5'-diphosphate (ADP) also inhibited I(Ca). The rank order of potency was ATP=UTP>ADP>2-MeSATP=alpha,beta-MeATP. 4. The P2 purinoceptor antagonists, suramin and pyridoxal-5-phosphate-6-azophenyl-2', 4'-disulfonic acid (PPADS), partially antagonized the ATP-induced inhibition of I(Ca), while coapplication of suramin and the P1 purinoceptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), virtually abolished I(Ca) inhibition. DPCPX alone partially antagonized I(Ca) inhibition. 5. Suramin antagonized the UTP-induced inhibition of I(Ca), while DPCPX had no effect. 6. Extracellular application of adenosine (ADO) also inhibited I(Ca) in a voltage-dependent manner via G(i/o)-protein activation. 7. Mainly N- and P/Q-type VDCCs were inhibited by both ATP and ADO via G(i/o)-protein betagamma subunits in seemingly convergence pathways.

• Authors: Mitsuhiro Abe, Takayuki Endoh, Takashi Suzuki
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 138 Issue 8 Pg. 1535-43 (Apr 2003) ISSN: 0007-1188 [Print] England
• PMID: 12721109 (Publication Type: Journal Article)

Chemical References

• Calcium Channels
• Receptors, Purinergic P1
• Receptors, Purinergic P2
• Adenosine Triphosphate

Topics

• Adenosine Triphosphate (metabolism, pharmacology)
• Animals
• Calcium Channels (metabolism)
• Cricetinae
• Dose-Response Relationship, Drug
• Extracellular Fluid (drug effects, metabolism)
• Ganglia, Parasympathetic (drug effects, metabolism)
• Male
• Neurons (drug effects, metabolism)
• Receptors, Purinergic P1 (metabolism)
• Receptors, Purinergic P2 (metabolism)
• Submandibular Gland (drug effects, metabolism)