Evidence for dopaminergic co‐transmission in dog mesenteric arterial vessels

Abstract

1 The overflow of dopamine and noradrenaline (NA) from the main trunk of the dog mesenteric artery and its proximal branches during prolonged depolarization (120min) by K+ (52imM) was quantified by high performance liquid chromatography with electrochemical detection. 2 K+-induced depolarization resulted in release of both dopamine and NA. The amount of NA released from both blood vessels declined progressively throughout the experiment. In the main trunk the same pattern of release was observed for dopamine, whereas in the proximal branches the overflow of dopamine increased throughout the experiment. 3 The addition of phentolamine (0.2 pM) to the perifusion fluid increased the overflow of both amines. In the presence of sulpiride (1 pM) the overflow of dopamine and NA was found to be increased in the proximal branches, but not in the main trunk. The addition of phentolamine to sulpiride caused a further increase in amine overflow in proximal branches, but not in the main trunk. 4 The addition of a-methyl-p-tyrosine (50 uM) to the perifusion fluid caused a decrease in the amounts of dopamine and NA released from both preparations. In a-methyl-p-tyrosine-treated preparations phentolamine increased amine overflow to the same extent as in experiments without tyrosine hydroxylase inhibition. The increasing effect of sulpiride on the overflow of dopamine and NA from the proximal branches was completely abolished after a-methyl-p-tyrosine. 5 The results presented suggest that in the proximal branches of the dog mesenteric artery, dopamine f-hydroxylase represents a rate limiting step in the synthesis of NA; dopamine, through activation of prejunctional dopamine receptors acts like a prejunctional co-transmitter in the control of transmitter release, but only newly-synthesized dopamine appears to be responsible for this effect.

Medicinal Chemistry of CatecholO-Methyltransferase (COMT) Inhibitors and Their Therapeutic Utility

“…The role of dopamine in the sympathetic nervous system is not limited only to providing a means for the synthesis of the neurotransmitter noradrenaline; 64 the amine can also act as a cotransmitter in some circumstances. 65 Non-neuronal cells capable of producing dopamine are distributed in the kidney and intestine. 66 These renal tubular and intestinal epithelial cells are endowed with a high capacity to synthesize dopamine from its immediate precursor, L-DOPA, where the amine plays a pivotal role as a local hormone with autocrine and paracrine function, regulating water and electrolyte homeostasis.…”

“…In the peripheral nervous system, dopamine is the first catecholamine in the biosynthesis of neurotransmitters such as norepinephrine and epinephrine. The role of dopamine in the sympathetic nervous system is not limited only to providing a means for the synthesis of the neurotransmitter noradrenaline; the amine can also act as a cotransmitter in some circumstances . Non-neuronal cells capable of producing dopamine are distributed in the kidney and intestine .…”

Fenoldopam as a Possible Medication for Non-Occlusive Mesenteric Ischemia (NOMI) and Contrast-Induced Nephropathy?

“…The basis behind NOMI's pathophysiology shows that by preserving blood supply to viscera, perfusion in mesenteric vessels is compromised; thus, in theory, a drug that can vasodilate these vessels can play a crucial role in providing sufficient perfusion to distressed vessels 2 . Prominent animal studies have shown that Fenoldopam acts as a vasodilator and increases blood flow in mesenteric arteries [3][4] .…”