Extracellular ATP-induced calcium channel inhibition mediated by P1/P2Y purinoceptors in hamster submandibular ganglion neurons.
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.
Department of Physiology, Tokyo Dental College, 1-2-2, Masago, Mihama-ku, Chiba 261-8502, Japan.
Mitsuhiro
M
Abe
Takayuki
T
Endoh
Takashi
T
Suzuki
D000255:Adenosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005726:Ganglia, Parasympathetic / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D013363:Submandibular Gland / Q000187:drug effects / Q000378:metabolism
D015220:Calcium Channels; D018047:Receptors, Purinergic P1; D018048:Receptors, Purinergic P2; D000255:Adenosine Triphosphate