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Pharmacological characterization of 5‐hydroxytryptamine‐induced hyperpolarization of the rat superior cervical ganglion
Author(s) -
Ireland S.J.,
Jordan C.C.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb11338.x
Subject(s) - hyperpolarization (physics) , spiperone , ketanserin , prazosin , superior cervical ganglion , phentolamine , medicine , endocrinology , chemistry , 5 ht receptor , antagonist , pharmacology , biology , receptor , stereochemistry , serotonin , nuclear magnetic resonance spectroscopy
1 A study has been made of the pharmacology of 5‐hydroxytryptamine (5‐HT)‐induced hyperpolarization responses recorded extracellularly from the rat isolated superior cervical ganglion (SCG). 2 Hyperpolarization responses induced by 5‐HT (1 × 10 −8 ‐1 × 10 −4 m ) in the presence of MDL 72222 (1 × 10 −5 m ) were not antagonized by phentolamine (1 × 10 −6 m ), prazosin (1 × 10 −7 ‐3 × 10 −7 m ), haloperidol (1 × 10 −6 m ) or ketanserin (1 × 10 −7 ‐1 × 10 −6 m ). However, the latter two compounds both potentiated and increased the persistence of the hyperpolarization induced by moderate to high concentrations of 5‐HT. Spiperone (1 × 10 −7 m ) caused similar effects. All further experiments were performed in the presence of ketanserin (1 × 10 −6 m ) as well as MDL 72222. 3 8‐Hydroxy‐2(di‐n‐propylamino)‐tetralin (8‐OH‐DPAT; 1 × 10 −7 ‐1 × 10 −4 m ) and ipsapirone (3 × 10 −5 ‐3 × 10 −4 m ) behaved as weak hyperpolarizing agonists on the SCG. However, at concentrations below those required to produce hyperpolarization, both compounds acted as unsurmountable antagonists of 5‐HT‐induced hyperpolarization. 4 5‐Carboxamidotryptamine (5‐CT; 1 × 10 −9 ‐1 × 10 −5 m ) mimicked the hyperpolarizing activity of 5‐HT on the SCG. The EC 50 for 5‐CT was approximately 9 fold lower than that for 5‐HT. 5 Spiperone (1 × 10 −7 ‐1 × 10 −5 m ) behaved as a reversible competitive antagonist of hyperpolarization responses induced by 5‐HT with a pK B value of 7.40 ± 0.09. Spiperone (1 × 10 −7 ‐1 × 10 −6 m ) also caused concentration‐dependent rightward displacement of the 5‐CT concentration‐hyperpolarization response curve. In this case, the pK B was 7.80 ± 0.05. 6 (±)‐Cyanopindolol (3 × 10 −7 ‐3 × 10 −6 m ) caused non‐parallel rightward displacements of the 5‐HT concentration‐response curve. Against 5‐CT, (±)‐cyanopindolol (3 × 10 −7 ‐3 × 10 −6 m ) caused a concentration‐independent rightward displacement of the concentration‐response curve, accompanied by a large increase in the maximum response. 5‐CT‐induced hyperpolarization recorded in the presence of (±)‐cyanopindolol (3 × 10 −7 m ) was not significantly antagonized by methiothepin (1 × 10 −6 m ) or methysergide (1 × 10 −6 m ). 7 It is concluded that 5‐HT‐induced hyperpolarization of the rat SCG is mediated via a 5‐HT 1 ‐like receptor which resembles the 5‐HT 1A binding site. However, a lack of selective drugs precludes more definitive characterization of this receptor.