Role of spinal NK1 receptors in cardiovascular responses to chemical stimulation of the gallbladder.
The present study examined the role of substance P (SP) as a sensory neurotransmitter in cardiovascular responses to bradykinin applied on the gallbladder. Experiments were performed in anesthetized cats in which sympathetic chains were transected at the T5-T6 level, and the tip of the intrathecal catheter was positioned at T6-T7 to limit the injectate between T6 and L2. Bradykinin (10 micrograms/ml) was applied onto the gallbladder before and after intrathecal injection of [D-Pro2,D-Phe7,D-Trp9]SP (100-200 micrograms, NK1/NK2-receptor antagonist), CP-99,994 (50-100 micrograms, selective NK1 antagonist), MEN-10,376 (100-500 micrograms, selective NK2 antagonist), or vehicle. Intrathecal injection of NK1 but not NK2 antagonist significantly reduced increases in mean arterial pressure, heart rate, and maximal rate of left ventricular pressure change by 28 +/- 2 mmHg (33 +/- 4%), 4 +/- 1 beats/min (42 +/- 5%), and 497 +/- 46 mmHg/s (36 +/- 4%), respectively. Intrathecal injection of NK1 or NK1/NK2 antagonist had no effect on cardiovascular responses evoked by electrical stimulation in the rostral ventral lateral medulla. These data suggest that endogenous SP, acting as a sensory neurotransmitter, is involved in the excitatory cardiovascular reflex caused by chemical stimulation of the gallbladder through its action on NK1 receptors in the spinal cord.
Pan
H L
HL
Department of Internal Medicine, University of California, Davis 95616.
Bonham
A C
AC
Longhurst
J C
JC
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002415:Cats; D004558:Electric Stimulation; D005260:Female; D005704:Gallbladder / Q000502:physiology*; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*; D013268:Stimulation, Chemical; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018040:Receptors, Neurokinin-1; C069192:neurokinin A(4-10), Tyr(5)-Trp(6,8,9)-Lys(10)-; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; C041817:substance P, Pro(2)-Phe(7)-Trp(9)-; D015288:Neurokinin A