Dopaminergic Regulation of Glandular Kallikrein in the Intermediate Lobe of the Rat Pituitary

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Abstract
The intermediate lobe of the rat pituitary contains a trypsin-like protease closely related or identical to glandular kallikrein. This study examined whether glandular kallikrein in the intermediate lobe is under inhibitory control by dopaminergic systems. Male rats were treated for 4-6 days with various doses of the following drugs, alone or in combination: haloperidol (a dopamine receptor blocker), reserpine (a catecholamine depleting agent), and bromocriptine (a dopamine receptor agonist). Neurointermediate lobe (NIL) homogenates were prepared. Following activation of latent enzymes with trypsin, glandular kallikrein was measured using two chromogenic peptide substrates. Haloperidol doubled NIL glandular kallikrein activity. Dissection of the NIL revealed that haloperidol specifically increased glandular kallikrein in the intermediate lobe and had no effect on the small amount of activity in the neural lobe. Reserpine also doubled NIL glandular kallikrein and haloperidol did not produce further increases. The reserpine-induced increase in NIL glandular kallikrein was completely blocked by concurrent administration of bromocriptine: this effect was blocked by haloperidol. The results demonstrate that intermediate lobe glandular kallikrein is under inhibitory control by dopaminergic systems. This parallels the regulation of proopiomelanocortin (POMC) synthesis in the intermediate lobe and suggests that glandular kallikrein should be evaluated as a POMC-processing enzyme.