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Adenosine inhibition via A 1 receptor of N‐type Ca 2+ current and peptide release from isolated neurohypophysial terminals of the rat
Author(s) -
Wang Gang,
Dayanithi Govindan,
Custer Edward E.,
Lemos José R.
Publication year - 2002
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2002.016394
Subject(s) - adenosine , chemistry , channel blocker , medicine , adenosine receptor , oxytocin , endocrinology , vasopressin , adenosine a1 receptor , receptor , biophysics , agonist , biochemistry , biology , calcium
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 μ m. Adenosine strongly inhibited, in a dose‐dependent manner (IC 50 = 2.67 μ m ), depolarization‐triggered AVP and OT release from isolated NH terminals. Adenosine and the N‐type Ca 2+ channel blocker ω‐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 ω‐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.