Identification in islets of Langerhans of a new rat alpha 2-adrenergic receptor.

Abstract

The islets of Langerhans are richly innervated, and an inhibitory effect on insulin secretion, mediated through alpha 2-adrenergic receptors, appears to be an important physiological neural modulator of beta-cell function. An alpha 2-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 alpha 2-receptor very similar to the human alpha 2-C2 receptor. No other alpha 2-receptor subtype was identified in normal islets by the PCR using alpha 2-receptor primers. This was also the only alpha 2-receptor subtype present in the exocrine pancreas and liver. In contrast, in the beta-cell line, beta TC3, the alpha 2-C2 receptor was not detected, but the alpha 2-C4 and alpha 2-C10 receptor subtypes were detected. It is suggested that the alpha 2-C2 subtype may be the principal alpha 2-receptor mediating inhibitory autonomic nervous system activity in the gastrointestinal tract. A comparison of the rat islet, pancreas, and liver alpha 2-receptor sequences reported here with previously reported alpha 2-receptor sequences indicates that the rat islet alpha 2-receptor is not the rat alpha 2-C2 homologue previously denoted as RNG alpha 2, but is a new, fourth rat subtype with an even higher similarity to the human alpha 2-C2 receptor.