Identification of the central tachykinin receptor subclass involved in substance P-induced cardiovascular and behavioral responses in conscious rats.
To identify the tachykinin receptor subclass involved in the central cardiovascular and behavioral actions of substance P (SP), we compared the central actions of SP with those of neurokinin A (NKA) and senktide in conscious chronically instrumented rats. Intracerebroventricular (i.c.v.) injection of SP (an NK1 agonist) and NKA (an NK2 agonist) increased mean arterial pressure (MAP) and heart rate (HR) dose dependently and these cardiovascular responses were associated with the behavioral responses, comprising excessive grooming and exploring. Both peptides were equipotent to produce the cardiovascular and the behavioral responses. Senktide (a highly selective NK-3 agonist), injected i.c.v. increased the HR markedly. The behavioral response, 'wet dog shakes', was observed most frequently after senktide and was dissociated from the HR response. Pretreatment with a peripheral NK-1-selective antagonist, L-668,169, attenuated the NKA-induced cardiovascular and behavioral responses but not the SP-induced responses. However, pretreatment with a peripheral NK-2-selective antagonists, L-659,877, attenuated the SP-induced responses but not the NKA-induced responses. These results suggest that the central cardiovascular and behavioral actions of SP and NKA are mediated by different subclasses of receptors and that the receptor subclasses which are specific for the central nervous system differ from those which mediate the peripheral actions of the two tachykinins.
Itoi
K
K
Department of Pharmacology, University of Heidelberg, Germany.
Tschöpe
C
C
Jost
N
N
Culman
J
J
Lebrun
C
C
Stauss
B
B
Unger
T
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D015288:Neurokinin A / Q000008:administration & dosage / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000032:analysis* / Q000037:antagonists & inhibitors / Q000187:drug effects; D018039:Receptors, Tachykinin; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D015320:Tachykinins / Q000378:metabolism*
D010446:Peptide Fragments; D017981:Receptors, Neurotransmitter; D018039:Receptors, Tachykinin; D015320:Tachykinins; C054724:senktide; D013373:Substance P; D015288:Neurokinin A