Structure-activity studies of the amine receptor on the Retzius cells of the leeches Hirudo medicinalis and Haemopis sanguisuga

1. The hyperpolarising (H) responses elicited by 5-hydroxytryptamine (5-HT) or dopamine (DA) on an amine receptor on Retzius (R) cells of two leech species (Hirudo medicinalis and Haemopis sanguisuga) were increased in duration but not amplitude by imipramine, suggesting the presence of an amine uptake system.2. A structure-activity study of twenty agonists was performed on this amine receptor, and equipotent molar ratio (e.p.m.r.) values calculated. DA and other compounds lacking the β-OH group on the ethylamine side chain were very potent. Compounds possessing a β-OH could produce D, H or biphasic responses although salbutamol was inactive. Substitution on the α-carbon or terminal nitrogen of the side chain reduced potency. Compounds required an -OH group on C4 of the phenyl ring. DA agonists were preferred in a β-rotational rather than an α-rotational conformation.3. There were no major differences between the responses of the two species to agonists, except that isoprenaline hyperpolarised Hirudo R cells but was inactive on Haemopis. E.p.m.r. values varied in the two species.4. Phentolamine acted as an antagonist in Haemopis but was inactive in Hirudo. In both species atropine was an effective antagonist.5. On the basis of this study a model is proposed for a joint DA-5-HT receptor in the leech.