Multiple actions of extracellular ATP and adenosine on calcium currents mediated by various purinoceptors in neurons of nucleus tractus solitarius.
Whole-cell patch-clamp recordings were performed on freshly dissociated nucleus tractus solitarius (NTS) of rat to determine the action of extracellular adenosine 5'-triphosphate (ATP) and adenosine (ADO) on voltage-dependent calcium channel (VDCC) currents (I(Ca)). Application of ATP and ATP-analog inhibited I(Ca). The rank order of potency of inhibition of I(Ca) was 2-methylthioATP (2-MeSATP) > ATP > adenosine 5'-diphosphate (ADP) >> alpha,beta-methylene ATP (alpha,beta-MeATP) = uridine 5'-triphosphate (UTP). Application of ADO receptor agonists also inhibited I(Ca). The rank order of potency of inhibition of I(Ca) was N(6)-cyclohexyladenosine (CHA) > ADO > 2-(4-(2-carboxyethyl)phenylethylamino)adenosine-5'-N-ethylcarboxamideadenosine (CGS-21680) > N(6)-2-(4-aminophenyl)ethyladenosine (APNEA). Application of prepulse attenuated these inhibition. Both intracellular dialysis of guanosin 5'-O-(2-thiodiphosphate) (GDP-beta-S) and anti-G(i) antibody also attenuated these inhibition. L-, N- and P/Q-type VDCCs were inhibited by ATP. In contrast, N- and P/Q-type VDCCs were inhibited by ADO. In addition to inhibition, application of 100 microM ATP facilitated I(Ca). Intracellular dialysis of GDP-beta-S did not attenuate these facilitations. In conclusion, activation of P2Y purinoceptors inhibits L-, N- and P/Q-types VDCCs via G(i)-protein betagamma subunits. Activation of A(1) and/or A(2) receptors inhibit N- and P/Q-types VDCCs via G(i)-protein betagamma subunits. Activation of P2X purinoceptors facilitates Ca(2+) entry in NTS.
Department of Physiology, Tokyo Dental College, 1-2-2 Masago, Mihama-ku, Chiba 261-8502, Japan.
Yoshihito
Y
Aoki
Emiko
E
Yamada
Takayuki
T
Endoh
Takashi
T
Suzuki
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D058913:Purinergic Agonists; D051381:Rats; D017208:Rats, Wistar; D011983:Receptors, Purinergic / Q000502:physiology*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology
D058913:Purinergic Agonists; D011983:Receptors, Purinergic; D000255:Adenosine Triphosphate; D000241:Adenosine