George E. Brown memorial lecture. Local modulation of adrenergic neurotransmission.
The cardiovascular reflexes, by regulating the traffic in the sympathetic nerves, govern the amount of norepinephrine released from the nerve endings. However, the final adjustments in the amount of neurotransmitter available to activate the beta 1 receptors in the heart and the alpha receptors in the blood vessels take place at the sympathetic neuroeffector junction. Thus, a decrease in pH, hyperosmolarity, moderate increases in the concentration of K+ ion, adenosine and adenine nucleotides depress the release of norepinephrine at any given level of sympathetic nerve activity. These metabolic changes, which occur in active tissues, and in particular in adenosine, have been proposed as mediators of the accompanying local hyperemia. In addition, they apparently facilitate this local dilatation by disconnecting the blood vessels in the active tissues from sympathetic control. Acetylcholine, histamine and 5-hydroxytryptamine are present in and around certain blood vessels and can activate specific receptors on the prejunctional fibers and cause vasodilatation by reducing the output of neutrotransmitter. Some of the norepinephrine released into the synaptic cleft may depress its continued release by activating prejunctional alpha receptors. In contrast, angiotensin II, by a local action on the nerve endings, can augment the release of transmitter. Decreases in local temperature reduce transmitter release but augment the affinity of the postjunctional alpha receptors for norepinephrine. The role of these local events at the neuroeffector junction, their physiologic significance and potential clinical importance are discussed in this review.
D000109:Acetylcholine / Q000097:blood; D000138:Acidosis / Q000378:metabolism; D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D009119:Muscle Contraction; D009411:Nerve Endings / Q000378:metabolism; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha; D012701:Serotonin / Q000494:pharmacology; D013566:Sympathomimetics / Q000494:pharmacology*; D009435:Synaptic Transmission; D013696:Temperature; D014664:Vasodilation
D000227:Adenine Nucleotides; D011942:Receptors, Adrenergic, alpha; D013566:Sympathomimetics; D000804:Angiotensin II; D012701:Serotonin; D006632:Histamine; D000241:Adenosine; D000109:Acetylcholine; D011188:Potassium