Prostaglandins and the Release of the Adrenergic Transmitter

Abstract

Prostaglandins (PG) are synthesized from arachidonic acid, which is deesterified from tissue lipids in response to various stimuli including adrenergic transmitter, consequent to activation of one or more lipase(s). The profile of arachidonic acid metabolites generated in response to sympathetic nerve stimulation or administration of norepinephrine (NE) may vary in different tissues. For example, in the kidney and spleen, PGE2, is the major and PGI2 and PGF2 alpha the minor products; whereas in the heart and blood vessels, PGI2 is the principal product of arachidonic acid generated in response to sympathetic nerve stimulation. PGE2 and PGI2 inhibit release of NE and/or the postjunctional actions of this neurotransmitter in several tissues. These observations and the findings that inhibitors of cyclooxygenase enhance NE release and the response of effector organs to nerve stimulation suggest that PGs act as physiological modulators of adrenergic transmission. The mechanism by which PGs modulate release of the adrenergic transmitter has not yet been established. NE appears to be released from sympathetic fibers during depolarization by influx of Na+, which is associated with entry of Ca++ through omega-conotoxin-sensitive Ca++ channels that are distinct from those in the vascular smooth muscle, which are sensitive to nifedipine. Ouabain in low external K+ activates the former, whereas external Na+ depletion activates the latter type of Ca++ channels in the nerve fiber and promotes release of NE. PGs (PGE2) may inhibit release of NE from nerve fibers by interfering with the availability of Ca++ through these Ca++ channels or promoting efflux of Ca++ from the nerve terminal.

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of α1- and α2-adrenoceptors on renal sensory nerve fibers

“…There is considerable evidence for norepinephrine increasing PGE 2 release in both central and peripheral neural tissue (e.g., 35,44). Although not examined in the current studies, it is possible that the increase in ARNA produced by reflex increases in ERSNA is also modulated by PGE 2 limiting the release of norepinephrine via stimulation of presynaptic EP3 receptors.…”

Presynaptic BK type Ca2+-activated K+ channels are involved in prostanoid TP receptor-mediated inhibition of noradrenaline release from the rat gastric sympathetic nerves

“…Prostanoids have been shown to modulate noradrenaline release from central and peripheral noradrenergic nerves (Starke et al, 1989;Malik and Sehic, 1990). In a previous study, we reported that prostanoid TP receptors located on the sympathetic nerve terminals mediate the inhibition of electrically evoked noradrenaline release from the rat stomach .…”

Role of Ca2+-activated K+ channels and Na+,K+-ATPase in prostaglandin E1- and E2-induced inhibition of the adrenergic response in human vas deferens

“…The mechanisms whereby PGE 1 and PGE 2 modify neurotransmitter release have received much attention but remain poorly understood. Prostaglandins of the E series inhibit transmitter release by an action on stimulussecretion coupling and more specifically on the availability of Ca 2+ for the release mechanism [8].…”