Substance P suppresses the activity of alpha 2-adrenoceptors of the nucleus reticularis gigantocellularis involved in cardiovascular regulation in the rat.
We evaluated possible interactions between substance P (SP) and the alpha 2-adrenoceptors in the nucleus reticularis gigantocellularis (NRGC) of the medulla oblongata involved in cardiovascular regulation. Adult, male Sprague-Dawley rats anesthetized with pentobarbital sodium (40 mg/kg, i.p., with 10 mg/kg/h i.v. supplements) were used. The circulatory suppressant efficacy of a centrally acting alpha 2-adrenoceptor agonist, guanabenz, was used as the experimental index. Bilateral microinjection of SP (300 or 600 pmol) into the NRGC, a medullary site that is critically involved in the cardiovascular depressive actions of guanabenz, significantly diminished the hypotensive and bradycardiac efficacy of the aminoguanidine compound (100 micrograms/kg, i.v.). This implied reduction in alpha 2-adrenoceptor activity in the NRGC by SP was antagonized by its selective receptor antagonist, [D-Pro2,D-Trp7,9]-SP (1200 pmol). Similarly, attenuation by SP of the cardiovascular suppressant effects of guanabenz was also reversed by immunocytochemically verified depletion of dopamine-beta-hydroxylase-immunoreactive nerve terminals in the NRGC, elicited by the selective noradrenergic neurotoxin, DSP4 (50 micrograms). These data suggest that SP may exert an inhibitory action on the alpha 2-adrenoceptors in the NRGC that are involved in central cardiovascular regulation, possibly via a presynaptic modulation on noradrenergic neurotransmission.
Len
W B
WB
Department of Medical Research, Veterans General Hospital-Taipei, Taiwan, Republic of China.
Tsou
M Y
MY
Chan
S H
SH
Chan
J Y
JY
D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D001931:Brain Mapping; D006143:Guanabenz / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007262:Infusions, Intravenous; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008845:Microinjections; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D012016:Reference Values; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013997:Time Factors
D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D013373:Substance P; C032132:substance P, prolyl(2)-tryptophan(7,9)-; D006143:Guanabenz