Lack of interaction between thyrotropin releasing hormone and its analogs with 3H-quinuclidinyl benzilate recognition sites in the rat striatum.

The effects of thyrotropin releasing hormone (TRH) on the binding of 3H-quinuclidinyl benzilate (QNB) to cholinergic muscarinic receptors of striatal region of rat brain were evaluated. In vitro studies indicate that neither TRH, its two analogs, MK-771 [L-N-(2-oxopiperidin-6-yl-carbonyl)-L-histidyl-L-thiazolidine-4-++ +carboximide] and DN-1417 (gamma-butyrolactone- gamma-carbonyl-L-histidyl-L-prolineamide) nor the metabolite histidyl-proline diketopiperazine [cyclo(His-Pro)] at concentrations ranging from 10(-9) to 10(-3) M affected 3H-QNB binding to striatal muscarinic receptors. On the other hand, p-Glu-His-Pro-OH (TRH-free acid), another metabolite of TRH caused significant inhibition (21%) at 10(-4) M concentration. Intraperitoneal administration of TRH (1 or 10 mg/kg) also failed to elicit any changes in the affinity (Kd) or density (Bmax) of muscarinic receptors in the striatum. The results suggest that TRH does not influence striatal muscarinic receptors and that the known effects of TRH and its analogs on central cholinergic system may be due to mechanisms other than those affecting postsynaptic muscarinic receptors directly.