The islets of Langerhans are richly innervated, and an inhibitory effect on insulin secretion, mediated through α2-adrenergic receptors, appears to be an important physiological neural modulator of β-cell function. An α2-receptor was cloned from isolated newborn rat islets using a polymerase chain reaction (PCR) approach. This receptor was shown by sequencing to be a new rat α2-receptor very similar to the human α2-C2 receptor. No other α2-receptor subtype was identified in normal islets by the PCR using os-receptor primers. This was also the only α2-receptor subtype present in the exocrine pancreas and liver. In contrast, in the β-cell line, βTC3, the α2-C2 receptor was not detected, but the α2-C4 and α2-C10 receptor subtypes were detected. It is suggested that the α2-C2 subtype may be the principal α2-receptor mediating inhibitory autonomic nervous system activity in the gastrointestinal tract. A comparison of the rat islet, pancreas, and liver α2-receptor sequences reported here with previously reported α2-receptor sequences indicates that the rat islet α2-receptor is not the rat α2-C2 homologue previously denoted as RNGα2, but is a new, fourth rat subtype with an even higher similarity to the human α2-C2 receptor.

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