5-HT1D receptors in guinea-pig and pigeon brain

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Abstract
The characteristics of high affinity [3H]5-HT (5-hydroxytryptamine) binding to non 5-HTIA non 5-HT1A sites were examined in crude membranes prepared from different regions of guinea-pig and pigeon brains. The coupling of these sites to adenylate cyclase was examined, and its pharmacological profile investigated. In the presence of 100 nmol/1 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) and 100 nmol/l mesulergine, [3H]5-HT labelled with nanomolar affinity an apparently homogeneous population of recognition sites in guinea-pig and pigeon brain membranes. The rank order of affinities of agonists and antagonists (5-CT (5-carboxamidotryptamine) > 5-HT > RU 24969 pyridinyl)-1H indole succinate) > yohimbine ≥ rauwolscine > DP-5-CT (N,N dipropyl-5-carboxamidotryptamine) ≥ mianserin > 8-OH-DPAT > mesulergine > SDZ 21-009 ((±)-4(3-tert-butyl-amino-2-hydroxypropoxy)-in-dol-2 carbonic acid isopropyl ester) > (-)propranolol), as well as their individual pKD values, were very similar to those at porcine caudate 5-HT1D sites and clearly different from those at rat cortex 5-HT1B sites. In the substantia nigra of the guinea-pig the 5-HT receptor-mediated inhibition of forskolin-stimulated adenylate cyclase had a pharmacological profile fully comparable to that of 5-HT1D binding sites (5-CT > 5-HT > yohimbine > RU 24969 > 8-OH-DPAT > SDZ 21-009 = isamoltane > (−)pindolol > (−)propranolol). The rank order of potency of agonists and antagonists in this system closely paralleled their corresponding rank order of potency in the calf substantia nigra (5-HT1D), but was clearly different from that in rat substantia nigra (5-HT1B) These results demonstrate the existence of 5-HT1D recognition sites in the guinea-pig and pigeon brain and their similarity to 5-HT1D sites of higher mammals, in terms of both drug affinity profile and second messenger coupling. No evidence of the presence of 5-HTIB sites was obtained. The present findings also suggest that 5-HT1D sites may be present in the brain of the majority of vertebrate species located higher than the sauropside-mammalian divergence in the phylogenic tree, whereas 5-HT1B sites are only found in some (e.g., mouse, rat, hamster) but not in other rodents (e.g. guinea-pig).