TY - JOUR
T1 - The sea anemone purine, caissarone
T2 - Adenosine receptor antagonism
AU - Cooper, Roland A.
AU - De Freitas, JoséCarlos
AU - Porreca, Frank
AU - Eisenhour, Cynthia M.
AU - Lukas, Ronald
AU - Huxtable, Ryan J.
PY - 1995/8
Y1 - 1995/8
N2 - Caissarone, a sea anemone iminopurine, produced an increase in the twitch response of the electrically stimulated guinea-pig ileum-myenteric plexus. In the same assay, caissarone reduced the inhibitory response to the endogenous neuromodulator, adenosine, the A1 adenosine receptor agonist, R-phenylisopropyladenosine (r-PIA), and the A2 agonist, 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA) in a dose-dependent manner. Schild plot analysis of antagonism by caissarone yielded slopes of near unity, indicating that caissarone acts as a simple competitive antagonist at the adenosine receptor. The dissociation constants (KB) for caissarone ranged from 0.53 mM to 0.78 mM. In functional nicotinic receptor assays in two human cell lines, caissarone failed either to potentiate or to reduce carbamylcholine-mediated 86Rb+ efflux. Thus, the enhancing activity of caissarone on the gut could not be attributed to activity at the ganglionic nicotinic receptor. Based on structure and pharmacological activity, caissarone appears to be the first marine product described as an adenosine receptor antagonist.
AB - Caissarone, a sea anemone iminopurine, produced an increase in the twitch response of the electrically stimulated guinea-pig ileum-myenteric plexus. In the same assay, caissarone reduced the inhibitory response to the endogenous neuromodulator, adenosine, the A1 adenosine receptor agonist, R-phenylisopropyladenosine (r-PIA), and the A2 agonist, 5′-(N-cyclopropyl)-carboxamidoadenosine (CPCA) in a dose-dependent manner. Schild plot analysis of antagonism by caissarone yielded slopes of near unity, indicating that caissarone acts as a simple competitive antagonist at the adenosine receptor. The dissociation constants (KB) for caissarone ranged from 0.53 mM to 0.78 mM. In functional nicotinic receptor assays in two human cell lines, caissarone failed either to potentiate or to reduce carbamylcholine-mediated 86Rb+ efflux. Thus, the enhancing activity of caissarone on the gut could not be attributed to activity at the ganglionic nicotinic receptor. Based on structure and pharmacological activity, caissarone appears to be the first marine product described as an adenosine receptor antagonist.
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U2 - 10.1016/0041-0101(95)00047-P
DO - 10.1016/0041-0101(95)00047-P
M3 - Article
C2 - 8533136
AN - SCOPUS:0029163107
SN - 0041-0101
VL - 33
SP - 1025
EP - 1031
JO - Toxicon
JF - Toxicon
IS - 8
ER -