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5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity

Pharmacological comparison with special reference to the effects of yohimbine, rauwolscine and some β-adrenoceptor antagonists

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Summary

5-Hydroxytryptamine1B (5-HT1B) receptor mediated-inhibition of forskolin-stimulated adenylate cyclase activity in rat substantia nigra was characterized pharmacologically and compared to 5-HT1D receptor mediated-inhibition of forskolin-stimulated adenylate cyclase activity in calf substantia nigra. Special attention was paid to the effects of drugs known to bind with high affinity to 5-HT1B (pindolol, propranolol, cyanopindolol, SDZ 21-009, isamoltane) or 5-HT1D recognition sites (yohimbine, rauwolscine).

PEC50 or pK B values of a variety of 5-HT-receptor ligands (6 agonists including 5-HT, and 12 antagonists) for the inhibition of adenylate cyclase activity in rat substantia nigra, correlated significantly to the corresponding pK D values at 5-HT1B binding sites (r = 0.90, P = 0.0001). Amongst the α2- and β-adrenoceptor antagonists tested, none of the drugs expressed more than 35% of the intrinsic activity of 5-HT at 5-HT1B receptors. When tested as antagonists, their pK B values were in good agreement with their pK D values for 5-HT1B sites. By contrast, these drugs displayed marked intrinsic activity at 5-HT1D receptors: their pEC50 values were close to their pK D values for 5-HT1D sites and their effects could be potently antagonized by methiothepin. The rank orders of potency of the tested compounds at 5-HT1B and 5-HT1D were markedly different.

The results strengthen the identity between 5-HT receptors mediating inhibition of adenylate cyclase activity in rat and calf substantia nigra and 5-HT1B and 5-HT1D binding sites, respectively. They underline the differences between these receptors in terms of intrinsic activities and potencies of drugs.

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  1. Preclinical Research, Sandoz Ltd, Bldg 386/525, CH-4002, Basel, Switzerland

    Philippe Schoeffter & Daniel Hoyer

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  1. Philippe Schoeffter
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Schoeffter, P., Hoyer, D. 5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity. Naunyn-Schmiedeberg's Arch Pharmacol 340, 285–292 (1989). https://doi.org/10.1007/BF00168512

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