Localization of specific binding sites for atrial natriuretic factor in the central nervous system of rat, guinea pig, cat and human.
Specific, high-affinity binding sites for atrial natriuretic factor (ANF) were identified and localized in the rat and guinea pig central nervous system (CNS), the cat brainstem, and the rat, guinea pig, cat and human spinal cord using quantitative autoradiographic techniques. The radioligands tested were rat 125I-ANF(1-28) in guinea pig, rat, cat and human tissues, human 125I-ANF in rat and human, and rat [3H]atriopeptin III in rat. All 3 radioligands labeled essentially the same structures in the brain and spinal cord of all species in which they were tested. In guinea pig very high concentrations of ANF binding sites were observed in the olfactory bulb, lateral olfactory tract and the granule cell layer of the cerebellum, high concentrations were observed in the fasciculus retroflexus, interpeduncular nucleus and subfornical organ. Moderate concentrations were observed in the nucleus accumbens, dorsomedial and suprachiasmatic hypothalamic nuclei, paraventricular thalamic nuclei, primary olfactory cortex and the subcommissural organ. High concentrations of ANF binding sites were also observed in the choroid plexus and the leptomeninges. Low concentrations were observed in the pineal gland. In the rat the same structures were labeled as in the guinea pig except that suprachiasmatic and dorsomedial hypothalamic nuclei, paraventricular thalamus and cerebellum were unlabeled. In the lower brainstem of the cat and all levels of the rat, guinea pig, cat and human spinal cord, the only site where specific binding was observed was in the pia/arachnoid. These findings suggest that ANF binding sites constitute several functional classes in the CNS as well as in a variety of other tissues. Outside the blood-brain barrier binding sites are prominent in glandular tissues implicated in the production of hormones involved in fluid and electrolyte balance, e.g. adrenal glomerulosa, neurohypophysis and subfornical organ, unstratified epithelia involved in ion gradient exchange, e.g. renal glomerulus, ciliary body, choroid plexus and pia mater; crossing the blood-brain barrier are sites in the anterior hypothalamus, e.g. organum vasculosum, regions of the brain parenchyma associated with angiotensin II binding sites, e.g. dorsomedial nucleus of hypothalamus, some of which may be occupied by brain rather than cardiac synthesized ANF, regions of brain lacking an obvious role in fluid and ion exchange or regulation, e.g. cerebellum, although association with K+,Na+-ATPase in guinea pig cerebellum may be a relevant clue and brain regions possibly implicated in an integrative and/or indirect regulatory role in fluid and electrolyte balance.(ABSTRACT TRUNCATED AT 400 WORDS)
Mantyh, CR; Kruger, L; Brecha, NC; Mantyh, PW
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