Central catecholamine-neuropeptide Y interactions at the pre- and postsynaptic level in cardiovascular centers.
Central catecholamine (CA)-neuropeptide Y (NPY) interactions and their regulation by glucocorticoids have been analyzed in vivo and in vitro, especially in the dorsal cardiovascular center of the medulla oblongata, including the nucleus tractus solitarius (nTS), using immunocytochemical, receptor autoradiographical, biochemical, and physiological techniques. Intraventricular (i.v.t.) injections of NPY in a low (7.5 pmol) or a high (1.25 nmol) dose increased adrenaline levels 4 h later in the caudal part of the dorsomedial medulla. Furthermore, NPY immunoreactivity (IR) tended to decrease in the rostral part of the dorsomedial medulla 5 min after injection of clonidine (1 microgram) in the alpha-chloralose anaesthetized rat. Thus, presynaptic interaction between NPY and adrenaline (A) mechanisms may exist in the dorsal cardiovascular center taking place at the network local circuit level or the membrane level of the NPY/A costoring synapses of the dorsomedial medulla. In vitro NPY (10 nM) reduced the affinity of the alpha 2-adrenergic agonist binding sites in the nTS, and clonidine (10 nM) reduced the 125I-NPY binding in the dorsomedial medulla. These results indicate the existence of postsynaptic receptor-receptor interactions between alpha 2-adrenergic and NPY receptors in the dorsal cardiovascular center. This interaction may in part take place at the level of the Ni protein, since NPY (300 nM) inhibited cyclic AMP (cAMP) accumulation in slices of the dorsomedial medulla. However, the interactions also probably take place at the proteins carrying the recognition sites, since NPY and adrenaline together given i.v.t. significantly antagonized the hypotensive effects of one another. Thus, the reduced affinity of the alpha 2-adrenergic receptor induced by NPY may reflect a reduced efficiency of this receptor and not an increased coupling of Ni protein to the adenylate cyclase. Thus, the postsynaptic interaction between the two receptors represents inter alia a sensitivity regulation of the two receptors. Evidence is also presented for the existence of a glucocorticoid regulation of NPY IR neurons, especially of those innervating the locus coeruleus, since after 2 weeks adrenalectomy reduced NPY IR in this area. Furthermore, glucocorticoid receptor IR was demonstrated in the nuclei of NPY nerve cell bodies of the nTS. Thus, glucocorticoids exert direct actions on cardiovascular NPY/CA costoring neurons, actions that may contribute to their hypertensive effects in humans.(ABSTRACT TRUNCATED AT 400 WORDS)
Fuxe
K
K
Department of Histology, Karolinska Institutet, Stockholm, Sweden.
Härfstrand
A
A
Agnati
L F
LF
Kalia
M
M
Fredholm
B
B
Svensson
T
T
Gustafsson
J A
JA
Lang
R
R
Ganten
D
D
D000818:Animals; D001345:Autoradiography; D002319:Cardiovascular System / Q000294:innervation*; D000242:Cyclic AMP / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000276:immunology / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000276:immunology; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000378:metabolism
D009478:Neuropeptide Y; D011942:Receptors, Adrenergic, alpha; D011965:Receptors, Glucocorticoid; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D000242:Cyclic AMP; D004837:Epinephrine