Possible Interaction: Niacin and Substance P

“The rapidity and the degree of the changes in SPLI after nicotine exceed those previously reported for other agents and implicate substance P neurotransmission as a major component of nicotinic action.”

“However, such treatment with SP enhanced nicotinic responses evoked by local pressure ejections of ACh (10 mM, 10- to 100-ms duration) in 77% of intracardiac neurons studied (n = 52).”

“ SP is known to have the following two effects on nicotine‐induced secretion of catecholamines (see Livett and Zhou, 1991): inhibition of the nicotinic response and protection against nicotinic desensitization.”

“Although agonists specific for either nicotinic or muscarinic receptors stimulated release of NE, SP selectively inhibited the nicotinic component of transmitter secretion.”

“6 At a higher concentration (10−5m), SP inhibited total nicotinic CA secretion throughout S1 and produced a biphasic secretion of CA (depressed in the presence of SP and enhanced after wash out of SP).”

“In addition to the ability of SP to increase or decrease the total amount of adrenal CA secretion, dependent on the concentration of SP, the present study shows that SP can change the time‐course of nicotinic CA secretion.”

“We suggest that SP protects some receptors from nicotinic desensitization while holding them in an inactive state, and that upon removal of SP these receptors can slowly respond to DMPP.”

“Previous studies show that SP has an inhibitory effect on the nicotinic response in a number of different tissue preparations.”

“These results suggest that SP facilitates CA secretion from the adrenal gland at two levels: (1) pre‐synaptically by facilitating ACh release from splanchnic nerve terminals, and (2) post‐synaptically by modulating the nicotinic secretory response by protection against nicotinic desensitization of secretion.”

“At low concentrations, up to 3 microM, SP partially inhibited or partially protected the nicotine response by 15-20%, and at high concentrations (30 microM), SP markedly inhibited or markedly protected the nicotinic response by 80 or 92%, respectively.”

“It is concluded that SP is more potent at protecting against desensitization than at inhibiting the nicotinic response and that SP might modulate CA release through activation of two receptor subtypes.”

“ SP exhibited biphasic effects in its actions of inhibiting the nicotinic secretory response and protecting against desensitization.”

“The action of SP was significantly reduced by pretreatment with muscarinic and nicotinic cholinergic, dopamine and histamine (H1) receptor antagonists.”

“This suggests that the previously reported ability of SP to modulate nicotinic receptor function in vitro by either inhibiting the nicotinic response or protecting against nicotinic desensitization may be more than a mere pharmacological curiosity.(ABSTRACT TRUNCATED AT 400 WORDS)”