Subtype switching of ANP receptors during in vitro culture of vascular cells

Vascular receptors for atrial natriuretic peptide (ANP) have been characterized immunochemically and found to be classified into two subtypes that show differential localization and expression. An antiserum, recognizing the protein core of the receptor, was raised against the purified bovine lung ANP receptor and used for the immunochemical subtyping. ANP receptors solubilized from the bovine jugular vein reacted strongly with the antiserum as well as the homologous lung receptor; however, the receptors from the aorta and carotid artery were recognized only weakly, indicating the presence of two types of ANP receptor in the vascular system. The one that reacts strongly with the antiserum and is distributed mainly in the venous side is termed type I and the other reacting weakly and predominating in the arteries, type II. The two subtypes were also distinguishable in their ligand specificities; the type I receptor showed a remarkably higher affinity for the ANP analogue atriopeptin I than the type II receptor. Surprisingly, similar immunochemical and biochemical analysis of the receptors on cultured vascular smooth muscle and endothelial cells revealed that the arterial cells originally expressing the type II receptor begin to express the type I receptor when cultured in vitro.

Respiratory arrhythmias and airway CO2, lung receptors, and central inspiratory activity

The purpose of this study was to determine whether hypocapnia affects heart rate secondary to an effect on pulmonary receptors. Dogs were anesthetized and placed on cardiopulmonary bypass. Interrelationships among airway CO2, central inspiratory activity, and lung receptor effects on respiratory-related heart rate changes (respiratory arrhythmias) were studied after vagal efferent activity was increased secondary to baroreceptor stimulation. Hypocapnia, isolated to the lungs, produced an increase in the magnitude of the respiratory arrhythmias observed. Two mechanisms may produce these results. Hypocapnia affects pulmonary receptors, which 1) reflexly alter heart rate and 2) modulate breathing frequency, thus altering the dynamics of the respiratory arrhythmias that were produced. The results also suggested that the reflex increase in heart rate in response to lung inflation and the Hering-Breuer expiratory-facilitatory reflex are either produced by different pulmonary receptors or by the same pulmonary receptors but may be mediated by different central mechanisms.

Glucocorticoids and hypothyroidism modulate development of fetal lung insulin receptors

We investigated the development of insulin receptors in membranes of fetal rabbit lung during normal ontogeny and the effect of glucocorticoids and hypothyroidism. Specific binding of 125I-insulin to fetal lung membranes increased progressively to a peak at 29 days gestation, declining by 30 days. Scatchard plots were curvilinear and revealed a progressive increase in receptor numbers (X 10(10)/mg protein) from 129 +/- 7 (mean +/- SE) at 22-24 days to 575 +/- 16 at 29 days, declining to 467 +/- 12 at 30 days, term being approximately 31 days. Affinities did not change throughout gestation and were similar to those of adult lung; receptor numbers in adults were significantly lower than in fetuses at 26-30 days. Epinephrine and PGE1 could evoke a doubling of cAMP production in adult and fetal lung membranes until 29 days. Concomitantly with the fall in fetal insulin receptor number at 30 days, cAMP production in response to epinephrine or PGE1 increased fivefold. Induction of fetal hypothyroidism decreased insulin receptor numbers in the lung of the 28-day fetus by 70% from control (P less than 0.001) without a change in receptor affinity. In contrast, betamethasone administration increased fetal lung insulin receptor numbers by 250% (P less than 0.001) but did not alter their affinity; maternal lung insulin receptors were not altered. Thus, normal ontogeny of the fetal lung insulin receptor is characterized by a progressive increase in number followed by decline immediately before parturition associated with a sharp increase of cAMP responsiveness of the membranes. Hypothyroidism and glucocorticoid exposure can modulate the normal development of the fetal lung insulin receptor.