Adenosine inhibition via A(1) receptor of N-type Ca(2+) current and peptide release from isolated neurohypophysial terminals of the rat.
Effects of adenosine on voltage-gated Ca(2+) channel currents and on arginine vasopressin (AVP) and oxytocin (OT) release from isolated neurohypophysial (NH) terminals of the rat were investigated using perforated-patch clamp recordings and hormone-specific radioimmunoassays. Adenosine, but not adenosine 5'-triphosphate (ATP), dose-dependently and reversibly inhibited the transient component of the whole-terminal Ba(2+) currents, with an IC(50) of 0.875 microM. Adenosine strongly inhibited, in a dose-dependent manner (IC(50) = 2.67 microM), depolarization-triggered AVP and OT release from isolated NH terminals. Adenosine and the N-type Ca(2+) channel blocker omega-conotoxin GVIA, but not other Ca(2+) channel-type antagonists, inhibited the same transient component of the Ba(2+) current. Other components such as the L-, Q- and R-type channels, however, were insensitive to adenosine. Similarly, only adenosine and omega-conotoxin GVIA were able to inhibit the same component of AVP release. A(1) receptor agonists, but not other purinoceptor-type agonists, inhibited the same transient component of the Ba(2+) current as adenosine. Furthermore, the A(1) receptor antagonist 8-cyclopentyltheophylline (CPT), but not the A(2) receptor antagonist 3, 7-dimethyl-1-propargylxanthine (DMPGX), reversed inhibition of this current component by adenosine. The inhibition of AVP and OT release also appeared to be via the A(1) receptor, since it was reversed by CPT. We therefore conclude that adenosine, acting via A(1) receptors, specifically blocks the terminal N-type Ca(2+) channel thus leading to inhibition of the release of both AVP and OT.
Wang
Gang
G
Department of Physiology and Neuroscience Program, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Dayanithi
Govindan
G
Custer
Edward E
EE
Lemos
José R
JR
D000241:Adenosine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D001464:Barium / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009411:Nerve Endings / Q000502:physiology*; D010121:Oxytocin / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010904:Pituitary Gland, Posterior / Q000502:physiology*; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D018047:Receptors, Purinergic P1 / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives* / Q000494:pharmacology
D020864:Calcium Channels, N-Type; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D001127:Arginine Vasopressin; D001464:Barium; C053907:8-cyclopentyl-1,3-dimethylxanthine; D010121:Oxytocin; D000255:Adenosine Triphosphate; D013806:Theophylline; D000241:Adenosine