An analysis of action of nicotinic agents on adrenergic nerve terminals in rat isolated vas deferens

Nicotine and DMPP caused contraction of rat isolated vas deferens. The contractile response was antagonized by hexamethonium, m, phenoxybenzamine, phentolamine, guanethidine and bretylium, but not by atropine. The response was absent in tissues depleted of their norepinephrine content. Nicotine enhanced the outflow of tritium from tissues preloaded with ³H-norepinephrine. Only 50% of the nicotine-induced tritium outflow was due to unchanged norepinephrine, the rest were due to five metabolites of norepinephrine, chiefly glycol derivatives. As tissues, at the time of exposure to nicotine contained almost all of the tritium in the form of unchanged norepinephrine, it is likely that norepinephrine, only after being released from storage sites by nicotine was acted upon by the catabolizing enzymes to form various metabolites. Desensitization and cross desensitization phenomena were observed to both nicotine and DMPP. The tissues desensitized to nicotine were, however, responsive to norepinephrine, tyramine and transmural stimulation.