Pharmacological characterization of 5-hydroxytryptamine-induced hyperpolarization of the rat superior cervical ganglion

Abstract

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 X 10(-8)-1 X 10(-4) M) in the presence of MDL 72222 (1 X 10(-5) M) were not antagonized by phentolamine (1 X 10(-6) M), prazosin (1 X 10(-7)-3 X 10(-7) M), haloperidol (1 X 10(-6) M) or ketanserin (1 X 10(-7)-1 X 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 X 10(-7) M) caused similar effects. All further experiments were performed in the presence of ketanserin (1 X 10(-6) M) as well as MDL 72222. 3 8-Hydroxy-2(di-n-propylamino)-tetralin (8-OH-DPAT; 1 X 10(-7)-1 X 10(-4) M) and ipsapirone (3 X 10(-5)-3 X 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 X 10(-9)-1 X 10(-5) M) mimicked the hyperpolarizing activity of 5-HT on the SCG. The EC50 for 5-CT was approximately 9 fold lower than that for 5-HT. 5 Spiperone (1 X 10(-7) - 1 X 10(-5) M) behaved as a reversible competitive antagonist of hyperpolarization responses induced by 5-HT with a pKB value of 7.40 +/- 0.09. Spiperone (1 X 10(-7)-1 X 10(-6) M) also caused concentration-dependent rightward displacement of the 5-CT concentration-hyperpolarization response curve. In this case, the pKB was 7.80 +/- 0.05. 6 (+/-)-Cyanopindolol (3 X 10(-7)-3 X 10(-6) M) caused non-parallel rightward displacements of the 5-HT concentration-response curve. Against 5-CT, (+/-)-cyanopindolol (3 X 10(-7)-3 X 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 X 10(-7) M) was not significantly antagonized by methiothepin (1 X 10(-6) M) or methysergide (1 X 10(-6) M). 7. It is concluded that 5-HT-induced hyperpolarization of the rat SCG is mediated via a 5-HT1-like receptor which resembles the 5-HT1A binding site. However, a lack of selective drugs precludes more definitive characterization of this receptor.