Tachykinin Agonists Modulate Cholinergic Neurotransmission at Guinea-Pig Intracardiac Ganglia

Abstract

Abstract. Effects of substance P (SP) and selective tachykinin agonists on neurotransmission at guinea-pig intracardiac ganglia were studied in vitro. Voltage responses of neurons to superfused tachykinins and nerve stimulation were measured using intracellular microelectrodes. Predominant effects of SP (1 µM) were to cause slow depolarization and enable synaptic transmission at low intensities of nerve stimulation. Augmented response to nerve stimulation occurred with 29 of 40 intracardiac neurons (approx. 73%). SP inhibited synaptic transmission at 23% of intracardiac neurons but also caused slow depolarization. Activation of NK 3 receptors with 100 nM [MePhe 7 ]neurokinin B caused slow depolarization, enhanced the response of many intracardiac neurons to low intensity nerve stimulation or local application of acetylcholine, and triggered action potentials independent of other stimuli in 6 of 42 neurons. The NK 1 agonist [Sar 9,Met(O 2 ) 11 ]SP had similar actions but was less effective and did not trigger action potentials independently. Neither selective agonist inhibited cholinergic neurotransmission. We conclude that SP can function as a positive or negative neuromodulator at intracardiac ganglion cells, which could be either efferent neurons or interneurons. Potentiation occurs primarily through NK 3 receptors and may enable neuronal responses with less preganglionic nerve activity. Inhibition of neurotransmission by SP is most likely explained by the known blocking action of this peptide at ganglionic nicotine receptors.

The Neurochemical Characterization of Parasympathetic Nerve Fibers in the Porcine Uterine Wall Under Physiological Conditions and After Exposure to Bisphenol A (BPA)

“…These substances probably play roles as neuromodulators, because their influence on cholinergic transmission has been reported. For example, GAL inhibits cholinergic neurotransmission in the heart (Potter and Smith-White 2005 ); SP increases the responsiveness of intestinal muscles to acetylcholine (Li et al 2014 ), modulates cholinergic neurotransmission within intra-cardiac ganglia (Zhang et al., Zhang et al 2005 ), and together with CGRP modulates the function of nicotinic receptors on autonomic neurons (Di Angelantonio et al 2003 ). Meanwhile, VIP enhances both the postjunctional effect of acetylcholine and the release of this mediator from nerve varicosities (Burnstock 2013 ).…”

Degeneration of vagal efferent axons and terminals in cardiac ganglia of aged rats

“…Within the heart, different cardiac ganglia control different functions (e.g., heart rate, A‐V conduction, and myocardial contractility) in dogs and cats (Rabdall and Ardell,1985; Randall et al,1986,1987,1996; McGuirt et al,1997; Massari et al,1998; Ardell,2004; Gray et al,2004a,b; Johnson et al,2004; Parsons,2004; Zhang et al,2005). In contrast to the conventional concept that cardiac ganglia are simple relay stations for the central nervous system input, these structures are more likely operating as complex integration centers (Randall et al,1996; Randall,2000; Armour,2004).…”

Input-output signal processing plasticity of vagal motorneurons in response to cardiac ischemic injury

“…Neurokinins and atrial natriuretic peptide in the gut induce the release of the same four peptides mentioned above along with several others [43][44][45][46][47][48] . Apart from action at the gut, both tachykinins and ANP have well-described effects on the heart including decreased heart rate 49,50 , coronary artery vasodilation 51 , and potentiation of acetylcholine signaling 52,53 . Further, the combination of norepinephrine and ANP likely works on post ganglionic neurons in the heart to mediate sympathoinhitibiton that was once thought to require input from at least two different neurons [54][55][56] , but we now show may plausibly come from the same vagal preganglionic neurons.…”