Inhibition by colchicine of carbamylcholine induced glycoprotein secretion by the submaxillary gland. A possible mechanism of cholinergic induced protein secretion

Abstract

During recent years, our knowledge about protein secretion by exocrine glands and the pathway of intracellular transport of these proteins increased considerably, thanks, chiefly to studies on the parotid [l] and the pancreas [2-71.These proteins are synthesized on ribosomes attached to the membrane of the rough endoplasmic reticulum (RER), segregated within the cisternae of the RER, then transferred via the Golgi apparatus and packaged into condensing vacuoles, which are transformed into zymogen granules.Finally the proteins are discharged from these granules into the acinar lumina.Palade's studies indicated 2 energy requiring locks in the course of this intracellular transport: the first lock connects the cisternae of RER and the condensing vacuoles whereas the second lock concerns the discharge of zymogen granules.The latter process is regulated by cholinergic agonists [6] in the pancreas.However, overall mucin secretion by submaxillary glands is induced by cholinergic and adrenergic transmitters (mainly norepinephrine).These stimulations are calcium dependent [8], this cation plays an active role in general secretory mechanisms : Douglas and Rubin [9] showed that the acetylcho~ne induced secretion of catecholamines, in the adrenal medulla, was also Ca2+ dependent.After a period of perfusion with Ca2+ free medium, when Ca2+ was added to the perfusate itself, a discharge of catechol~~es was evoked.Moreover, microtubules seem to be involved in secretory mechanisms as reported by Lacy et al. [ 101, North-Holland Publishing Company -Amsterdam * Preliminary results which are not reported in the present work indicate that dibutyrylcyclic GMP is inactive on mucin secretion and metabolic events.Whereas dibutyrylcyclic AMP stimulates both glycoprotein biosynthesis and secretion.