Opioid Peptides in the Rabbit Carotid Body: Identification and Evidence for Co-Utilization and Interactions with Dopamine

Abstract: The rabbit carotid body is a catecholaminergic organ that contains dopamine and norepinephrine in a proportion of nearly 5:1. Chronic (15 days) carotid sinus nerve denervation or superior cervical ganglionectomy did not modify the carotid body dopamine content (5–6 nmol/mg of protein, equivalent to 250 pmol per carotid body), but sympathectomy reduced by ～ 50% the norepinephrine content. The carotid body has also a very high content of opioid activity (250 equivalent pmol of Leu-enkephalin/mg of protein) as measured by a radioreceptor assay that detects preferentially δ-opioid activity. In the carotid body the degree of opioid posttranslational processing to low-molecular-weight peptides (mostly Leu- and Met-enkephalin) is nearly 80%. HPLC identification of opioid peptides revealed that the sequences of Met- and Leu-enkephalin were in a proportion of nearly 6:1, indicating that the main opioid precursor in the carotid body is proenkephalin A. Chronic denervations of the carotid body did not modify the levels or the degree of opioid precursor processing. Acute hypoxic exposure of the animals (8% 0₂ in N₂; 3 h) resulted in a parallel decrease of dopamine and opioid activity, without any change in the degree of opioid processing. Norepinephrine levels were not affected by hypoxia. These findings suggest corelease of dopamine and opioids during natural hypoxic stimulation. In agreement with the analytical data. [d -Ala², d -Leu⁵]enkephalin, but not [d -Ala²,N-Me-Phe⁴ Gly⁵-ol]-enkephalin, reduced the in vitro release of dopamine induced by low Po₂, a high external K⁺ concentration, and dinitrophenol. Naloxone augmented the release response elicited by low Po₂ stimulation. These findings indicate that the previously described inhibitory actions of opioids are mediated, at least in part, by receptors located in chemoreceptor cells. Additional targets for opioid peptides, e.g., sensory nerve endings or blood vessels, and additional actions of opioids on chemoreceptor cells, e.g., long-term trophic actions, are not excluded.