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Reciprocal interactions between α2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat

A biochemic and autoradiographic analysis

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Summary

Interactions between a α2-adrenoreceptor agonist and neuropeptide Y (NPY) binding sites have been studied in the rat medulla oblongata (MO) using biochemical binding techniques as well as quantitative autoradiography. Tritiated para-amino clonidine (3H-PAC; α2-adrenoceptor agonist), idazoxan (3H-IDA; α2-adrenoceptor antagonist) and iodinated neuropeptide Y (125I-NPY) were used as radioligands. (1) Neuropeptide Y (NPY; 10−8M) but not bovine pancreatic polypeptide (BPP) nor peptide YY (PYY 10nM) increased the KD value of3H-PAC binding sites. However, intraventricular administration of a high dose of NPY (1.25nmol) did not change the3H-PAC binding characteristics in MO membrane preparations of these animals. (2) GTP 10−4 lowered the affinity of3H-PAC binding. NPY (10 nM) had no additional effect, nor did NPYinfluence the GTP induced shift in potency of clonidine to displace3H-IDA from its binding sites. (3) In the autoradiographical experiments NPY (10nM) significantly reduced3H-PAC binding (2nM) in the nucleus tractus solitarius (NTS) area by 35%. (4) When clonidine, either given centrally in vivo (3.75nmol) or in vitro (10 nM) the binding of125I-NPY was reduced (34 and 24%, respectively) in the NTS. When the monoamine receptors were irreversibly blocked in vivo by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ, 10 μg i.e. 24h)125I-NPY (0.5 nM) binding was increased by 137% in the NTS. This effect of EEDQ was prevented by pretreatment with the α2-adrenoreceptor antagonist idazoxan.

These results provide support for a direct intramembrane interaction between the α2-receptor and the NPY receptor within the NTS and may be of importance in central cardiovascular regulation.

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  1. A. Härfstrand

    Present address: AB, Department of Biology, Pharmacia Ophthalmics, S-75182, Uppsala, Sweden

Authors and Affiliations

  1. Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden

    A. Härfstrand & K. Fuxe

  2. Department of Human Physiology, University of Modena, Modena, Italy

    L. Agnati

  3. Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden

    B. Fredholm

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Härfstrand, A., Fuxe, K., Agnati, L. et al. Reciprocal interactions between α2-adrenoceptor agonist and neuropeptide Y binding sites in the nucleus tractus solitarius of the rat. J. Neural Transmission 75, 83–99 (1989). https://doi.org/10.1007/BF01677422

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