Violeta Mutafova-Yambolieva M.D., Ph. D.
Contact Violeta Mutafova-Yambolieva M.D., Ph. D.
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My laboratory is interested in understanding how the peripheral nervous system regulates the functions of blood vessels and visceral smooth muscles. We investigate pre-junctional and post-junctional aspects of neurotransmission including mechanisms of co-neurotransmitter release and neuromodulation, intercellular communications at the neuro-effector junction, and signal transduction pathways underlying neurotransmitter action. Our long-term goal is to develop methods for the prevention and treatment of conditions associated with dysfunction of the peripheral nervous system such as hypertension, abnormal vasospasm, cardiogenic shock, congestive heart failure, neurogenic bladder, and gastro-intestinal motility disorders.
Recently, we determined that beta-nicotinamide adenine dinucleotide (NAD) is released along with norepinephrine (NE) and adenosine 5'-triphosphate (ATP) during nerve stimulation in blood vessels and visceral smooth muscles from a large variety of species as well as in brain neurons. NAD, not previously considered a player at the neuroeffector junction, appears to meet several criteria defining a neurotransmitter and neuromodulator. In some systems, NAD mimics the endogenous purine neurotransmitter better than ATP, thus adding novel perceptions to the concept of plurichemical neurotransmission. Moreover, our most recent research suggests that multiple purine nucleotides, including "primary" purines such as NAD and ATP, as well as their immediate or distant metabolites, could also be involved in neurotransmission. The next logical step is to determine the functional correlates of these phenomena using models corresponding to physiological and pathological conditions in humans. We use neurochemistry, protein biochemistry, immunohistochemistry, functional and molecular biology techniques to study mechanisms of neurotransmission from mice with specific gene deletions, to genetically hypertensive animals, to human and non-human primates. This work has occasioned stimulating collaborations with other investigators in the department, the school and other places in the USA.
- Durnin L, VN Mutafova-Yambolieva. . Cyclic ADP-ribose (cADPR) requires CD38 to regulate the release of adenosine 5’-triphosphate (ATP) in visceral smooth muscle. FEBS Journal, 271:3095-3108
- Hwang SJ, Durnin L, Dwyer L, Rhee PL, Ward SM, Koh SD, Sanders KM, and VN Mutafova-Yambolieva. . -nicotinamide adenine dinucleotide is an enteric inhibitory neurotransmitter in human and nonhuman primate colons. ß. Gastroenterology, 140: 608-617.e6
- Smyth LM, Yamboliev IA, VN Mutafova-Yambolieva. . N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and ß-NAD in blood vessels. Neuropharmacology, 56(2):368-378
- Yamboliev IA, Smyth LM, Durnin L, Dai Y-P, VN Mutafova-Yambolieva. . Storage and secretion of ß-NAD, ATP and dopamine in NGF-differentiated rat pheochromocytoma PC12 cells. European Journal of Neuroscience, 30:756-768
- Mutafova-Yambolieva VN, Hwang SJ, Hap X, Chen H, Zhu MX, Wood JD, Ward SM, Sanders KM. . ß-nicotinamide adenine dinucleotide is a new inhibitory neurotransmitter in visceral smooth muscle. Proceedings National Academy of Sciences USA, 104(41):16359-64
- Bobalova J, Mutafova-Yambolieva VN. . Activation of the adenylyl cyclase/protein kinase A pathway facilitates neural release of beta-nicotinamide adenine dinucleotide in canine mesenteric artery. Eur J Pharmacol 536:128-32
- Bobalova J, VN Mutafova-Yambolieva. . Activation of the adenylyl cyclase-protein kinase A pathway facilitates neural release of ß-nicotinamide adenine dinucleotide (ß-NAD) in canine mesenteric artery. European Journal of Pharmacology, 536, 128-132
- Breen LT, Smyth LM, Yamboliev IA, Mutafova-Yambolieva VN. . beta-NAD is a novel nucleotide released on stimulation of nerve terminals in human urinary bladder detrusor muscle. Am J Physiol Renal Physiol 290:F486-95
- Smyth LM, Breen LT, Mutafova-Yambolieva VN. . Nicotinamide adenine dinucleotide is released from sympathetic nerve terminals via a botulinum neurotoxin A-mediated mechanism in canine mesenteric artery. Am J Physiol Heart Circ Physiol 290(5):H1818-25
- Smyth LM, Breen LT, Yamboliev IA, Mutafova-Yambolieva VN. . Novel localization of CD38 in perivascular sympathetic nerve terminals. Neuroscience 139:1467-77
- Yamboliev IA, Mutafova-Yambolieva VN. . PI3K and PKC contribute to membrane depolarization mediated by alpha2-adrenoceptors in the canine isolated mesenteric vein. BMC Physiol. 15;5:9
- Smyth LM, Bobalova J, Mendoza MG, Lew C, Mutafova-Yambolieva VN. . Release of beta-nicotinamide adenine dinucleotide upon stimulation of postganglionic nerve terminals in blood vessels and urinary bladder. Biol Chem 279:48893-903
- Mutafova-Yambolieva VN, Smyth L, Bobalova J.. . Involvement of cyclic AMP-mediated pathway in neural release of noradrenaline in canine isolated mesenteric artery and vein. Cardiovasc Res 57:217-24
- Bobalova J, Bobal P, Mutafova-Yambolieva VN. . High-performance liquid chromatographic technique for detection of a fluorescent analogue of ADP-ribose in isolated blood vessel preparations. Anal Biochem 305:269-76
- Bobalova J, Mutafova-Yambolieva VN. . Corelease of endogenous ATP and NA in guinea-pig vein exceeds corelease in mesenteric artery. Clin Exp Pharmacol Physiol 28:397-401
- Mutafova-Yambolieva VN, Keef KD. . Frequency dependent alpha2-adrenoceptor mediated modulation of excitatory junction potentials in guinea-pig mesenteric artery. Eur J Pharmacol 411/1-2, 125-129
- Bobalova J, Mutafova-Yambolieva VN. . Presynaptic alpha2-adrenoceptor mediated modulation of ATP and noradrenaline co-release: differences in canine mesenteric artery and vein. J Autonomic Pharmacol, 21: 1-9
- Smyth L, Bobalova J, Ward SM, Keef KD, Mutafova-Yambolieva VN. . Cotransmission from sympathetic vasoconstrictor neurons: differences in guinea-pig mesenteric artery and vein. Autonomic Neuroscience: Basic and Clinical, 86/1-2:18-29
- Smyth L, Bobalova, S. M. Ward, Mutafova-Yambolieva VN. . Neuropeptide Y is a cotransmitter with noradrenaline in guinea-pig inferior mesenteric vein. Peptides 21(6): 835-843
- Mutafova-Yambolieva VN. Carolan BM, Harden TK, Keef KD. . P2Y Receptors Mediate Contraction in Guinea-Pig Mesenteric Vein. Gen Pharmacol. The Vascular System. 34, 127-136
- Mutafova-Yambolieva VN, Westfall DP. . Effects of type-C Natriuretic Peptide (CNP) on Adrenergic/Purinergic Cotransmission in Rat Tail Artery. Clin Exp Pharmacol Physiol, 25, 12:1013-1018
- Mutafova-Yambolieva VN, Westfall DP. . Inhibitory and Facilitatory Presynaptic Effects of Endothelin on Sympathetic Cotransmission in the Rat Isolated Tail Artery. Br J Pharmacol, 123, 136-142
- Mutafova-Yambolieva VN, Keef KD. . Adenosine-induced hyperpolarization in guinea-pig coronary artery involves A2b receptors and KATP channels. Am J Physiol Heart Circ Physiol, 273, 42/6, H2687-H2695
- Durnin L, Dai YP, Aiba I, CW Shuttleworth, Yamboliev IA, VN Mutafova-Yambolieva. Release, neuronal effects and removal of extracellular ß-nicotinamide adenine dinucleotide (ß-NAD+) in the rat brain. European Journal of Neuroscience, In Press