Spinal subarachnoid injection of somatostatin causes neurological deficits and neuronal injury in rats.
The tetradecapeptide somatostatin produced dose-related neurological deficits following subarachnoid injection in the lumbar spinal cords of rats. Lower pharmacological doses (1.6 and 3.1 nmol, i.t.) of somatostatin caused only transient deficits, while higher doses (6.2-25 nmol, i.t.) caused persistent deficits characterized by motor and sensory impairments in hindlimbs and tail, hindlimb edema, priapism, bladder atony with infarction, and urinary incontinence. Pretreatment with 0.3 nmol of the somatostatin receptor antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)] blocked the hindlimb paralytic effects of 3.1 and 6.2 nmol of somatostatin, and significantly improved neurological recovery injection of 12.5 nmol of somatostatin. Higher doses of the antagonist produced hindlimb paralysis by itself. Neuroanatomical evaluations revealed extensive cell loss and necrosis in the lumbosacral spinal cords of rats paralyzed by 25 nmol of somatostatin. Collectively, these results suggest that through interactions with a receptor, somatostatin destroys neurons involved in diverse spinal cord functions.
D000818:Animals; D007267:Injections; D008297:Male; D009422:Nervous System Diseases / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects*; D004856:Postural Balance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D012018:Reflex / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000633:toxicity*; D013116:Spinal Cord; D013346:Subarachnoid Space
D013004:Somatostatin