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Agonist properties of pindolol at h5-HT1A receptors coupled to mitogen-activated protein kinase.

Millan MJ, Newman-Tancredi A, Duqueyroix D, Cussac D.
Eur J Pharmacol. 2001 Jul 13;424(1):13-7.

At h5-HT1A receptors, stably transfected into Chinese Hamster Ovary Cells (CHO-h5-HT1A), the selective 5-HT1A receptor agonist, (+)8-hydroxy-dipropyl-amino-tetralin, ((+)8-OH-DPAT), transiently activated mitogen-activated protein kinase (MAPK) with a pEC50 of 8.5. The arylalkylamine, (-)-pindolol, also behaved as an agonist with a maximal effect of 57% relative to (+)8-OH-DPAT (100%), and with a pEC50 of 7.2. The selective 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclo-hexane carboxamide (WAY100,635), blocked (+)8-OH-DPAT- and (-)-pindolol-induced MAPK activation with pK(B)s of 9.7 and 9.9, respectively, whereas the selective 5-HT(1B) receptor antagonist, 1'-Methyl-5-[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-ylcarbonyl]-2,3,6,7-tetrahydro-5H-spiro[furo[2,3-f]indole-3,4'-piperidine] (SB224,289) was inactive. Pertussis toxin blocked the actions of (+)8-OH-DPAT and (-)-pindolol demonstrating implication of G(i)/G(o) proteins. Thus, stimulation of MAPK provides an intracellular marker and signal for expression of the agonist actions of (-)-pindolol at h5-HT1A receptors.