Prostaglandins and the release of the adrenergic transmitter.
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.
Malik
K U
KU
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Sehic
E
E
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D002395:Catecholamines / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D011453:Prostaglandins / Q000494:pharmacology / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
D001095:Arachidonic Acids; D002395:Catecholamines; D018377:Neurotransmitter Agents; D011453:Prostaglandins; D016718:Arachidonic Acid; D009638:Norepinephrine